Published:  10 December 2015

Nitrofurantoin - Not Suitable In Renal Impairment

Prescriber Update 36(4): 51-52
December 2015

Key Messages

  • Nitrofurantoin is contraindicated in patients with creatinine clearance under 60 mL/min.
  • Adverse reactions to nitrofurantoin may occur with both acute treatment and prophylaxis of genitourinary infections.
  • Pulmonary reactions, both acute and chronic, are the most commonly reported adverse reaction.

Nitrofurantoin is indicated for the treatment and prophylaxis of susceptible genitourinary infections1. Since nitrofurantoin use can be short or long term there are well defined acute and chronic adverse reactions to treatment. Long-term use is up to six months unless the benefits clearly outweigh the risk.

The efficacy of nitrofurantoin is dependent on its concentration in the bladder. As renal function deteriorates, the nitrofurantoin bladder concentration decreases and plasma levels increase. Therefore, in renal impairment efficacy is reduced and the potential for adverse reactions increased. Nitrofurantoin is consequently contraindicated in patients with creatinine clearance less than 60 mL/min1.

The Centre for Adverse Reactions Monitoring (CARM) has received 333 adverse reaction reports up until 30 September 2015 where nitrofurantoin was considered a suspect medicine.

Respiratory symptoms are the most commonly reported adverse reaction (Table 1).

Table 1: Reported reaction type (by system organ class) to nitrofurantoin and onset time

System Organ Class <1 week >1 week
<1 month
>1 month Unknown Total
Respiratory 36 23 63 14 136
Skin and Appendages 72 17 6 4 99
Nervous System 19 9 25 3 56
Alimentary 39 9 4 2 54
Liver 7 5 22 4 38
Total reactions* 261 93 139 43 536

*not all system organ classes are shown therefore the total does not reflect the numbers in the table

Acute pulmonary reactions include fever, chills, cough, chest pain, dyspnoea, pulmonary infiltration, and eosinophilia1. Chronic pulmonary reactions include malaise, dyspnoea, cough, and diffuse interstitial pneumonitis or fibrosis or both1. If any of these pulmonary reactions occur, nitrofurantoin should be discontinued and the patient should be advised to seek medical attention.

Alimentary and skin reactions are mostly reported in the first week of nitrofurantoin use, whereas liver reactions generally occur after one month. Respiratory and nervous system reactions are reported at all the time periods analysed (Table 1).

The reaction onset time by age group is shown in Table 2. As expected, the number of reports increases with the age of the patient, likely due to greater use and greater susceptibility to adverse reactions. Both acute and chronic reactions are reported in all age groups, with the exception of those aged under 20 years.

Table 2: Nitrofurantoin adverse reaction onset time by age group

Age <1 week >1 week
<1 month
>1 month Unknown Total
<20 years 4 1 0 0 5
20-29 years 10 4 1 0 15
30-39 years 14 6 4 0 24
40-49 years 13 4 7 3 27
50-59 years 35 6 15 3 59
60-69 years 24 13 24 6 67
>70 years 44 18 59 14 135
Unknown 0 1 0 0 1
Total cases 144 (43%) 53 (16%) 110 (33%) 26 (8%) 333

Reports of pulmonary reactions were reviewed to determine whether reduced renal function was a risk factor for the reaction. However, most reports contained little to no information on renal function. Of the 136 reports of pulmonary reactions, 11 were reported to have pre-existing renal disease. None of the reports provided the patient's creatinine clearance.

The Medicines Adverse Reactions Committee (MARC) recently reviewed the available information on use of nitrofurantoin in patients with renal impairment ( The MARC considered that the benefits of nitrofurantoin treatment do not outweigh the risks of harm in patients with creatinine clearance less than 60 mL/min.

  1. W.M. Bamford & Company Limited. 2004. Nifuran Data Sheet 9 November 2004. (accessed 4 November 2015).