Nitrofurantoin oral suspension is contraindicated in:
- patients with known hypersensitivity to nitrofurantoin [see Warnings and Precautions ( 5.1 )].
- patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin [see Warnings and Precautions ( 5.3 )].
- patients who have anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) due to an increased risk of toxicity resulting from impaired excretion of the drug [see Warnings and Precautions ( 5.4 )].
- pregnant patients at term (38 weeks to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent and in pediatric patients younger than 1 month of age because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability) [see Warnings and Precautions ( 5.5 ) and Use in Specific Populations ( 8.1 and 8.4 )].
- Known hypersensitivity to nitrofurantoin. ( 4 )
- History of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin. ( 4 )
- Patients who have anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine). ( 4 )
- Pregnant patients at term (38 weeks to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. ( 4 )
- Pediatric Patients under one month of age. ( 4 )
AND PRECAUTIONS Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving nitrofurantoin oral suspension. If signs and symptoms of a hypersensitivity reaction occurs, immediately discontinue nitrofurantoin oral suspension. ( 5.1 )
Pulmonary
Reactions: Discontinue if sign and symptoms of pulmonary reactions occur and take appropriate measures. ( 5.2 ) Hepatotoxicity: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests. (5.3) Neuropathy: Peripheral neuropathy has occurred. ( 5.4 )
Hemolytic
Anemia: Discontinue if sign and symptoms of hemolysis occur. ( 5.5 ) Clostridioides difficile -associated diarrhea: Evaluate patients if diarrhea occurs. ( 5.6 )
5.1 Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving nitrofurantoin oral suspension <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span>. If signs and symptoms of a hypersensitivity reaction occurs, immediately discontinue nitrofurantoin oral suspension and initiate appropriate medications and/or supportive care. Nitrofurantoin oral suspension is contraindicated in patients with known hypersensitivity to nitrofurantoin.
5.2 Pulmonary Reactions Acute, subacute, or chronic pulmonary reactions have been reported in patients treated with nitrofurantoin oral suspension. If these reactions occur, discontinue nitrofurantoin oral suspension and take appropriate measures. Reports have cited pulmonary reactions as a contributing cause of death. Chronic pulmonary reactions (diffuse interstitial pneumonitis or pulmonary fibrosis, or both) can develop insidiously. These reactions occur generally in patients receiving therapy for six months or longer. Close monitoring of the pulmonary condition of patients receiving long-term therapy is warranted and requires that the benefits of therapy be weighed against potential risks <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span>.
5.3 Hepatotoxicity Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, has occurred. Fatalities have been reported. The onset of chronic active hepatitis may be insidious. Monitor patients periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, discontinue nitrofurantoin oral suspension immediately, and take appropriate measures.
5.4 Neuropathy Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating disease may enhance the occurrence of peripheral neuropathy. Monitor patients receiving long-term therapy periodically for changes in renal function. Optic neuritis has been reported with nitrofurantoin formulations <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> .
5.5 Hemolytic Anemia Cases of hemolytic anemia of the primaquine-sensitivity type have been induced by nitrofurantoin. Hemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. This deficiency is found in 10 percent of Blacks and a small percentage of ethnic groups of Mediterranean and Near-Eastern origin. If hemolysis occurs, discontinue nitrofurantoin oral suspension immediately; hemolysis ceases when the drug is withdrawn.
5.6 Clostridioides difficile -associated Diarrhea Clostridioides 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 . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and institute surgical evaluation as clinically indicated.
5.7 Persistence or Reappearance of Bacteriuria Nitrofurantoin lacks the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with nitrofurantoin oral suspension are predisposed to persistence or reappearance of bacteriuria. If persistence or reappearance of bacteriuria occurs with symptoms of urinary tract infection, after treatment with nitrofurantoin oral suspension, other therapeutic agents with broader tissue distribution should be selected. In considering the use of nitrofurantoin oral suspension, lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antibacterial resistance when agents with broader tissue distribution are utilized.
5.1 Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving nitrofurantoin oral suspension <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span>. If signs and symptoms of a hypersensitivity reaction occurs, immediately discontinue nitrofurantoin oral suspension and initiate appropriate medications and/or supportive care. Nitrofurantoin oral suspension is contraindicated in patients with known hypersensitivity to nitrofurantoin.
5.2 Pulmonary Reactions Acute, subacute, or chronic pulmonary reactions have been reported in patients treated with nitrofurantoin oral suspension. If these reactions occur, discontinue nitrofurantoin oral suspension and take appropriate measures. Reports have cited pulmonary reactions as a contributing cause of death. Chronic pulmonary reactions (diffuse interstitial pneumonitis or pulmonary fibrosis, or both) can develop insidiously. These reactions occur generally in patients receiving therapy for six months or longer. Close monitoring of the pulmonary condition of patients receiving long-term therapy is warranted and requires that the benefits of therapy be weighed against potential risks <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span>.
5.3 Hepatotoxicity Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, has occurred. Fatalities have been reported. The onset of chronic active hepatitis may be insidious. Monitor patients periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, discontinue nitrofurantoin oral suspension immediately, and take appropriate measures.
5.4 Neuropathy Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating disease may enhance the occurrence of peripheral neuropathy. Monitor patients receiving long-term therapy periodically for changes in renal function. Optic neuritis has been reported with nitrofurantoin formulations <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> .
5.5 Hemolytic Anemia Cases of hemolytic anemia of the primaquine-sensitivity type have been induced by nitrofurantoin. Hemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. This deficiency is found in 10 percent of Blacks and a small percentage of ethnic groups of Mediterranean and Near-Eastern origin. If hemolysis occurs, discontinue nitrofurantoin oral suspension immediately; hemolysis ceases when the drug is withdrawn.
5.6 Clostridioides difficile -associated Diarrhea Clostridioides 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 . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and institute surgical evaluation as clinically indicated.
5.7 Persistence or Reappearance of Bacteriuria Nitrofurantoin lacks the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with nitrofurantoin oral suspension are predisposed to persistence or reappearance of bacteriuria. If persistence or reappearance of bacteriuria occurs with symptoms of urinary tract infection, after treatment with nitrofurantoin oral suspension, other therapeutic agents with broader tissue distribution should be selected. In considering the use of nitrofurantoin oral suspension, lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antibacterial resistance when agents with broader tissue distribution are utilized.