Furadantin (Nitrofurantoin) - Drug Interactions, Contraindications, Overdosage, etc

Drug/laboratory Test Interactions

As a result of the presence of nitrofurantoin, a false-positive reaction for glucose in the urine may occur.  This has been observed with Benedict's and Fehling's solutions but not with the glucose enzymatic test.

OVERDOSAGE:

Occasional incidents of acute overdosage of Furadantin have not resulted in any specific symptoms other than vomiting.  Induction of emesis is recommended.  There is no specific antidote, but a high fluid intake should be maintained to promote urinary excretion of the drug.  It is dialyzable. 

CONTRAINDICATIONS:

Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications.  Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug.
 
Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38-42 weeks gestation), during labor and delivery, or when the onset of labor is imminent.  For the same reason, the drug is contraindicated in neonates under one month of age. 
 
Furadantin is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.  Furadantin is also contraindicated in those patients with known hypersensitivity to nitrofurantoin.
 
WARNINGS:
 
Pulmonary reactions:
ACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH NITROFURANTOIN.  IF THESE REACTIONS OCCUR, FURADANTIN SHOULD BE DISCONTINUED AND APPROPRIATED MEASURES TAKEN.  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 RARELY AND 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. (SEE RESPIRATORY REACTIONS.)
 
Hepatotoxicity:
Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely.  Fatalities have been reported.  The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury.  If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken. 
 
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.  Patients receiving long-term therapy should be monitored periodically for changes in renal function.
 
Optic neuritis has been reported rarely in postmarketing experience with nitrofurantoin formulations.
 
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.  Hemolysis is an indication for discontinuing Furadantin; hemolysis ceases when the drug is withdrawn.
 
Clostridium difficile- associated diarrhea:
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Furadantin Oral Suspension, 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 antimicrobial therapy and may require colectomy.  CDAD must be considered in all patients who present with diarrhea following antibiotic 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 antibiotic use not directed against C. difficile may need to be discontinued.  Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. 

REFERENCES

1. National Committee for Clinical Laboratory Standards.  Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically - Seventh Edition.  Approved Standard NCCLS Document M7-A4, Vol. 17, No. 2, NCCLS, Wayne, PA, January, 1997.
   
2. National Committee for Clinical Laboratory Standards.   Performance Standards for Antimicrobial Disk Susceptibility Tests  - Sixth Edition.  Approved Standard NCCLS Document M2-A6, Vol. 17, No. 1, NCCLS, Wayne, PA, January, 1997.