Published: 10 December 2015

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Nitrofurantoin - Not Suitable In Renal Impairment

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

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 (www.medsafe.govt.nz/profs/adverse/Minutes163.htm). 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.

References

1. W.M. Bamford & Company Limited. 2004. Nifuran Data Sheet 9 November 2004. URL:www.medsafe.govt.nz/profs/datasheet/n/Nifurantab.pdf (accessed 4 November 2015).