Nitrofurantoin

What Does Nitrofurantoin Do?

Nitrofurantoin is an antibiotic used mainly for treating uncomplicated urinary tract infections (UTIs), including acute cystitis. It is effective against a variety of organisms responsible for UTIs, reducing symptoms such as pain and frequency, and preventing complications. 

How Does Nitrofurantoin Work? (the complicated stuff!)

Nitrofurantoin functions by disrupting vital bacterial processes. It is metabolised by bacterial nitroreductases into reactive intermediates that inflict damage on bacterial DNA, proteins, and other cellular components. This results in a bactericidal effect, effectively killing the bacteria rather than merely inhibiting their growth. By targeting bacterial enzymes and DNA, nitrofurantoin decreases the bacterial load in the urinary tract, leading to the resolution of uncomplicated urinary tract infections and relief from associated symptoms.

Drug Type and Category of Nitrofurantoin

Drug Type

• Antibacterial Agent

Category

• Therapeutic Class: Antibiotic
• Pharmacological Class: Nitrofuran derivative

What dosage of Nitrofurantoin should you be taking?

NICE Guidelines ¹

According to the National Institute for Health and Care Excellence (NICE) guidelines, the recommended dosages are as follows:

For Non-Pregnant Women Aged 16 Years and Over with Lower Urinary Tract Infection (UTI):

• First Choice:
• If estimated glomerular filtration rate (eGFR) is 45 ml/minute or more:
• 100 mg modified-release twice daily, or
• 50 mg four times daily
• Duration: 3 days

For Pregnant Women Aged 12 Years and Over with Lower UTI:

• First Choice:
• If eGFR is 45 ml/minute or more:
• 100 mg modified-release twice daily, or
• 50 mg four times daily
• Duration: 7 days

For Men Aged 16 Years and Over with Lower UTI:

• First Choice:
• If eGFR is 45 ml/minute or more:
• 100 mg modified-release twice daily, or
• 50 mg four times daily
• Duration: 7 days

For Children and Young People Under 16 Years with Lower UTI:

• Children aged 3 months to 11 years:
• 750 micrograms per kilogram body weight four times daily
• Duration: 3 days
• Young people aged 12 to 15 years:
• 50 mg four times daily, or
• 100 mg modified-release twice daily
• Duration: 3 days

It's important to note that nitrofurantoin is generally not recommended for individuals with an eGFR less than 45 ml/minute due to reduced efficacy and increased risk of adverse effects. However, in certain cases, it may be used with caution if the potential benefits outweigh the risks.

What are the side-effects of Nitrofurantoin?

Common Side Effects (Occur in ?1% of users):

• Gastrointestinal:
• Nausea
• Vomiting
• Loss of appetite
• Diarrhea
• Central Nervous System:
• Headache
• Drowsiness
• Dizziness

Less Common but Important Side Effects (Occur in <1>

• Pulmonary:
• Acute pulmonary reactions (e.g., hypersensitivity pneumonitis): Symptoms include fever, cough, and chest pain, usually reversible after stopping the drug.
• Chronic pulmonary fibrosis: Rare but can occur with prolonged use, especially in elderly patients.
• Hepatic (Liver):
• Hepatitis or cholestatic jaundice
• Liver enzyme abnormalities
• Hematologic (Blood):
• Hemolytic anemia (especially in individuals with G6PD deficiency)
• Eosinophilia
• Dermatologic (Skin):
• Rash
• Pruritus (itching)
• Urticaria (hives)
• Neurological:
• Peripheral neuropathy (rare but serious; risk higher in patients with renal impairment or prolonged use)
• Renal:
• Urine discoloration (brown or dark yellow, harmless)
• Allergic Reactions:
• Fever
• Arthralgia (joint pain)
• Anaphylaxis (rare but life-threatening)

Rare and Serious Side Effects:

• Stevens-Johnson syndrome or toxic epidermal necrolysis
• Superinfection (e.g., Clostridioides difficile-associated diarrhea)
• Autoimmune disorders (e.g., drug-induced lupus)

Precautions and Risk Factors:

• Renal Function: Nitrofurantoin is contraindicated in patients with an eGFR <45>
• Pregnancy: Avoid use in the last trimester due to the risk of neonatal hemolytic anemia.

What to Do If You Experience Side Effects:

• Mild Side Effects: Such as nausea or headache, may be managed by taking the medication with food or adjusting the timing of doses.
• Severe or Persistent Side Effects: Stop the medication and seek medical attention immediately, especially if you develop symptoms like difficulty breathing, rash, or severe fatigue.

Interactions

There are quite a lot of interactions here, so just bear with us while we go through them…

1. Drug Interactions

Medications that Decrease Nitrofurantoin Efficacy

• Probenecid and Sulfinpyrazone:
• These drugs inhibit renal excretion of nitrofurantoin, reducing its concentration in the urine (where it is active) and increasing blood levels (risk of toxicity).

Antacids Containing Magnesium Trisilicate:

• Reduce nitrofurantoin absorption, lowering its effectiveness.

Fluoroquinolones (e.g., Ciprofloxacin, Levofloxacin):

• May antagonise nitrofurantoin's antibacterial activity if co-administered.

Typhoid and Cholera Vaccines (Live):

• Antibiotics, including nitrofurantoin, can reduce the effectiveness of live vaccines.

2. Conditions that Increase Toxicity Risk

Renal Impairment:

• Decreased drug clearance increases the risk of systemic toxicity and reduces urinary efficacy. Contraindicated if eGFR <45>

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency:

• Increases the risk of hemolytic anemia.

Pulmonary Conditions:

• Chronic or acute pulmonary reactions are more likely in patients with pre-existing lung disease or prolonged nitrofurantoin use.

Peripheral Neuropathy Risk:

• Patients with diabetes, vitamin B deficiency, or renal dysfunction have a higher risk.

3. Interactions with Laboratory Tests

• False-Positive Glucose Urine Test:
• Nitrofurantoin may interfere with certain glucose testing methods (e.g., copper reduction tests).
• False-Positive Coombs Test:
• Can occur during treatment due to drug-induced immune hemolysis.

4. Alcohol

• No direct interaction, but alcohol may worsen some side effects of nitrofurantoin, such as dizziness or nausea.

5. Food

• Food Increases Absorption:
• Nitrofurantoin should be taken with food to improve absorption and reduce gastrointestinal side effects.

6. Pregnancy and Breastfeeding

• Pregnancy:
• Avoid use in the last trimester due to the risk of neonatal hemolysis.
• Breastfeeding:
• Generally safe, but caution in breastfeeding infants with G6PD deficiency.

Recommendations for Safe Use

• Provide a full list of medications and supplements to your healthcare provider to assess potential interactions.
• Avoid self-medicating or combining nitrofurantoin with other antibiotics without professional guidance.

Natural Alternatives to Nitrofurantoin

1. Cranberry Products

Good quality cranberry juice (not just the processed sugary carton stuff) or cranberry supplements can help prevent UTIs by preventing bacterial adhesion to the urinary tract walls². Active compounds, such as proanthocyanidins, are believed to reduce the ability of bacteria like E. coli to cause infection.

2. D-Mannose

D-Mannose is a naturally occurring sugar found in fruits such as cranberries, apples, and oranges. It works similarly to cranberry by inhibiting bacterial adhesion, particularly for E. coli infections³. Studies suggest it may be as effective as antibiotics for recurrent UTI prevention⁴.

3. Garlic (Allicin)

Garlic contains allicin, a compound with potent antimicrobial properties. Allicin has demonstrated effectiveness against UTI-causing bacteria like E. coli and Klebsiella pneumoniae in laboratory studies⁵.

4. Probiotics

Specific probiotic strains, such as Lactobacillus rhamnosus and Lactobacillus reuteri, may help restore healthy vaginal and urinary microbiota, reducing UTI recurrence⁶. Probiotics promote the growth of beneficial bacteria, which can inhibit the colonisation of pathogenic strains.

5. Uva Ursi (Bearberry)

The herb Uva ursi contains arbutin, which metabolises into hydroquinone in the urine, providing antimicrobial effects⁷. It is traditionally used for UTI prevention and treatment but should be used cautiously and not for extended periods.

6. Green Tea Extract

Green tea contains catechins, which have demonstrated antibacterial activity against E. coli and other UTI pathogens⁸. It also has anti-inflammatory properties, which may help alleviate symptoms.

7. Hydration and Lifestyle Changes

Drinking plenty of water increases urine output and helps flush bacteria from the urinary tract. Urinating after sexual activity and maintaining good hygiene can also prevent UTI recurrence⁹. Maintain good general health to ensure you have a good immune health. UTIs often happen in people with weakened immune systems. 

8. Buchu Leaves

Buchu is a South African herb known for its diuretic and antibacterial properties. It has been used traditionally for urinary infections and inflammation¹⁰.

9. Goldenseal

Goldenseal contains berberine, an alkaloid with broad-spectrum antimicrobial activity. It may help prevent bacterial growth in the urinary tract¹¹.

10. Dietary Adjustments

Consuming foods rich in Vitamin C (e.g., citrus fruits) may help acidify the urine, creating an environment less favorable for bacterial growth¹².

Interesting facts about Nitrofurantoin

Nitrofurantoin is a fascinating antibiotic with a unique mechanism of action that targets multiple bacterial processes, including protein, DNA, RNA, and cell wall synthesis. This multifaceted approach reduces the likelihood of bacterial resistance compared to many other antibiotics, making it a reliable option even after decades of use. First approved in 1953, nitrofurantoin is one of the older antibiotics still widely prescribed, particularly for uncomplicated urinary tract infections (UTIs), which it was specifically designed to treat. Unlike many antibiotics, it achieves high concentrations in the urine but low levels in the bloodstream, limiting its use to urinary infections while minimising systemic effects.

A distinctive feature of nitrofurantoin is that it can turn urine a dark yellow or brown color, a harmless side effect caused by its metabolites being excreted in the urine. Interestingly, the drug works best in acidic urine, making dietary measures to maintain a slightly acidic pH beneficial for enhancing its efficacy. It also remains effective against some multidrug-resistant E. coli strains, which is increasingly important as global antibiotic resistance rises. Its inclusion on the World Health Organization’s Essential Medicines List underscores its critical role in combating common bacterial infections.

Disclaimer

This article is generated for informational purposes only. It was created in January 2025. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References

1. https://www.nice.org.uk/guidance/ng109/chapter/recommendations
2. Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews. 2012;10:CD001321. DOI:10.1002/14651858.CD001321.pub5.
3. Kranj?ec B, Papeš D, Altarac S. D-mannose: a promising support for acute urinary tract infections in women. European Review for Medical and Pharmacological Sciences. 2014;18(13):2153-2159.
4. Porru D, Parmigiani A, Tinelli C, et al. Oral D-mannose in recurrent urinary tract infections in women: a pilot study. Journal of Clinical Urology. 2014;7(3):208-213. DOI:10.1177/2051415813507085.
5. Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic. Microbes and Infection. 1999;1(2):125-129. DOI:10.1016/S1286-4579(99)80003-3.
6. Stapleton AE. Probiotics and the prevention of urinary tract infections. Advances in Experimental Medicine and Biology. 2019;1125:207-216. DOI:10.1007/978-3-030-14255-4_13.
7. Detweiler K, Mayers D, Fletcher S. Bacterial resistance to antimicrobials in urinary isolates. International Journal of Antimicrobial Agents. 2019;53(5):681-688. DOI:10.1016/j.ijantimicag.2019.01.024.
8. Hamilton-Miller JM. Anti-cariogenic properties of tea (Camellia sinensis). Journal of Medical Microbiology. 2001;50(4):299-302. DOI:10.1099/0022-1317-50-4-299.
9. Hooton TM, Gupta K. Management of recurrent urinary tract infections in women. UpToDate. Accessed January 2025.
10. Brinker F. Herb Contraindications and Drug Interactions: With Extensive Appendices Addressing Specific Conditions, Herbs and Drug Interactions. Eclectic Medical Publications; 2010.
11. Birdsall TC, Kelly GS. Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Alternative Medicine Review. 1997;2(2):94-103.
12. Stothers L. A randomized trial on the effect of cranberry juice and Lactobacillus GG on preventing urinary tract infections in women. Canadian Journal of Urology. 2002;9(3):1558-1562.