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The antibiotic nitrofurantoin (FURADANTIN, MACRODANTIN, MACROBID), approved by the Food and Drug Administration (FDA) only to treat urinary tract infections, has been listed as a Do Not Use drug since publication of the first edition of Worst Pills, Best Pills in 1988. This recommendation is based on a warning issued by the World Health Organization in 1985 that older adults should not use nitrofurantoin.
Nitrofurantoin, a very old drug first introduced into clinical medicine in 1953,...
The antibiotic nitrofurantoin (FURADANTIN, MACRODANTIN, MACROBID), approved by the Food and Drug Administration (FDA) only to treat urinary tract infections, has been listed as a Do Not Use drug since publication of the first edition of Worst Pills, Best Pills in 1988. This recommendation is based on a warning issued by the World Health Organization in 1985 that older adults should not use nitrofurantoin.
Nitrofurantoin, a very old drug first introduced into clinical medicine in 1953, is known to cause both acute and chronic pulmonary adverse reactions. One of the most serious adverse reactions associated with nitrofurantoin treatment, particularly its long-term use in the elderly, is a drug-induced lung disorder known as interstitial or pulmonary fibrosis that can leave the lungs irreversibly scarred.
The symptoms of acute pulmonary reactions with nitrofurantoin are fever, chills, cough, chest pain and difficulty breathing. Acute reactions usually occur within the first week of treatment with the drug and are reversible if treatment is stopped.
The New Zealand Centre for Adverse Reactions Monitoring (CARM) reviewed reports of nitrofurantoin-induced lung toxicity in May 2002 after receiving a report of fatal lung toxicity resulting from long-term nitrofurantoin treatment. The patient was a 67-year-old woman with a history of severe rheumatoid arthritis who developed a cough after 20 months of nitrofurantoin treatment taken for severe recurrent urinary tract infections. Nitrofurantoin was continued for a further six months before it was stopped when lung toxicity was diagnosed. She died three months later.
In the CARM database, 34 percent of the nitrofurantoin adverse reaction reports involve the respiratory system. Half of these reflect lung tissue damage, including nine reports of pulmonary fibrosis. Twenty-six reports for respiratory system adverse effects were the result of chronic nitrofurantoin treatment.
The FDA-approved professional product labeling, or “package insert,” for nitrofurantoin carries the warning in bold type regarding lung toxicity (see box below).
Nitrofurantoin should not be used in persons with significant impairment of kidney function. The excretion of the drug is inhibited in these patients, which can lead to an increased risk of toxicity. Because of the possibility that nitrofurantoin can cause a breakdown of red blood cells (hemolytic anemia), the drug should not be used in pregnant patients at term (38 to 42 weeks gestation), during labor and delivery or when the onset of labor is imminent. For the same reason, the drug is contraindicated in newborns less than one month of age.
Many patients who are treated with nitrofurantoin are predisposed to persistence or reappearance of bacteria in the urine because the drug is concentrated in the urine and is not as widely distributed in the body as other antibiotics approved for urinary tract infections. Urine specimens for culture and susceptibility testing should be obtained before and after completion of nitrofurantoin treatment. If persistence or reappearance of bacteria in the urine occurs after treatment with nitrofurantoin, other antibiotics with broader tissue distribution should be used.
Antacids containing magnesium trisilicate can interact when given together with nitrofurantoin to reduce both the rate and extent of absorption. The mechanism for this interaction probably is adsorption of nitrofurantoin onto the surface of magnesium trisilicate. Drugs such as probenecid (BENEMID) and sulfinpyrazone (ANTURANE) can inhibit the kidney’s ability to eliminate nitrofurantoin. The resulting increase in nitrofurantoin serum levels may increase toxicity, and the decreased urinary levels could lessen its effectiveness as a urinary tract antibacterial.
Adverse drug reaction reports suggest a higher proportion of lung reactions, including fatalities, in elderly patients. These differences appear to be related to the higher proportion of elderly patients receiving long-term nitrofurantoin treatment. As in younger patients, chronic lung reactions generally are observed in patients receiving treatment for six months or longer. Reports also suggest an increased proportion of severe liver toxicity, including fatalities, in elderly patients.
What You Can Do
Older adults should not use nitrofurantoin long term for the treatment of urinary tract infections.
If you develop the symptoms of acute lung toxicity listed above, contact your physician immediately.
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WARNINGS: |
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ACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH NITROFURANTOIN. IF THESE REACTIONS OCCUR, MACROBID SHOULD BE DISCONTINUED AND APPROPRIATE 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. |
