Urinary tract infections (UTIs) are one of the most common bacterial infections worldwide: a whopping 404.61 million cases were estimated to have occurred in 2019. Although various antibiotics can treat these infections, nitrofurantoin has long been a top choice for doctors when treating uncomplicated UTIs. It is often recommended as a first-line treatment in medical guidelines due to its effectiveness, low resistance rates, and minimal side effects.
This article will explain everything you need to know about nitrofurantoin, from how it works to how to use it safely while minimizing side effects.
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What Is Nitrofurantoin?
Nitrofurantoin is an FDA-approved antibiotic for treating lower UTIs (cystitis) and has been in clinical use since 1953. Its effectiveness and low potential for causing bacterial resistance make it a standard treatment option in current medical practice.
Nitrofurantoin is the generic version of the brand-name medications Macrobid®, Macrodantin®, and Furadantin®.
- Macrobid®: Available as 100 mg capsules. It contains nitrofurantoin macrocrystals and nitrofurantoin monohydrate, which work together to release the medication more slowly and prevent gastrointestinal side effects.
- Macrodantin®: Available as 25, 50, or 100 mg capsules. It contains only nitrofurantoin macrocrystals.
- Furadantin®: Available as an oral liquid suspension in concentrations of 25 mg/5 mL or 50 mg/5 mL.
Indications and Uses
Nitrofurantoin is FDA-approved to treat and prevent uncomplicated UTIs caused by susceptible strains of pathogenic bacteria residing in the urinary tract, including:
- Escherichia coli
- Enterococci
- Klebsiella
- Staphylococcus saprophyticus and aureus
- Enterobacter
How Nitrofurantoin Works
Nitrofurantoin works by disrupting the bacteria's ability to produce proteins and other molecules essential for their growth.
Mechanism of Action
After oral administration, nitrofurantoin is absorbed in the small intestine and enters the bloodstream. It is rapidly excreted by the kidneys into urine, where it is actively taken up by bacterial cells. Inside the bacterial cell, nitrofurantoin undergoes reduction by bacterial enzymes to form reactive metabolites or intermediates.
These intermediates are highly reactive. They bind to bacterial ribosomes, the machinery responsible for protein synthesis. This binding interferes with the synthesis of proteins, enzymes, and cell wall components, all of which bacteria need for growth, replication, and survival. By disrupting these metabolic processes, nitrofurantoin prevents bacteria from multiplying and ultimately leads to their death.
Benefits Over Other Antibiotics
Unlike other antibiotics traditionally used as first-line treatments for uncomplicated UTIs, such as trimethoprim-sulfamethoxazole, which are experiencing rising resistance rates, nitrofurantoin continues to have low resistance rates. This is likely due to its broad-based mechanism of action, which affects multiple bacterial processes.
Nitrofurantoin also has high solubility in urine, which allows it to achieve therapeutic concentrations in the urinary tract while maintaining low systemic levels. The advantage of this urinary concentration is twofold:
- It ensures that nitrofurantoin reaches bactericidal (bacteria-killing) levels in the urine, where it is needed to treat UTIs
- Low systemic levels minimize the risk of side effects
Dosage and Administration
The dosage information provided here is based on general guidelines. It is important to never adjust your dosage without consulting your doctor. Your healthcare provider will determine the appropriate dosage based on your specific health needs, medical history, and any other medications you may be taking.
Standard Dosages
Treatment for Adults:
- Macrobid® and Its Generic Form: 100 mg twice daily for five days
- Macrodantin® and Its Generic Form: 50 mg four times daily for five days
Prevention for Adults:
- 50-100 mg once daily
Treatment for Children:
- Macrobid® and Its Generic Form: Approved for children 12 years and older. Dose 100 mg twice daily for seven days.
- Macrodantin® and Its Generic Form: Approved for infants and children 1 month and older. Dose 5-7 mg/kg body weight divided into four equal doses daily for seven days.
- Furandantin® and Its Generic Form: Approved for infants and children 1 month and older. Dose 5-7 mg/kg body weight divided into four equal doses daily for seven days.
How to Take Nitrofurantoin
Nitrofurantoin should be taken with food to help your body absorb it better. Research shows that the drug's urinary concentrations increase by 40% when taken with food.
Taking it with food or milk can also help reduce gastrointestinal discomfort, one of nitrofurantoin's most commonly reported side effects.
Side Effects and Risks
Nitrofurantoin is generally considered safe, though, like any medication, it can cause side effects. The side effect profile of nitrofurantoin is well-documented, and patients should be aware of potential risks:
Common Side Effects
- Nausea
- Vomiting
- Diarrhea
- Loss of appetite
- Headache
- Dizziness
- Skin rashes or itching
Serious Risks
- Pulmonary Toxicity: Symptoms include fever, chills, cough, muscle pain, difficulty breathing, and dry cough.
- Liver Injury: Signs and symptoms include elevations in serum aminotransferase levels, jaundice (yellowing of the skin and whites of the eyes), hepatitis, and liver failure. Preexisting liver disease increases the risk of drug-induced liver toxicity.
- Peripheral Neuropathy: Nerve damage that presents as numbness, tingling, weakness, or burning in the hands and feet. This is mainly associated with prolonged use in patients with poor kidney function.
- Hemolytic Anemia: A condition where red blood cells are destroyed faster than they can be produced. Symptoms include fatigue, pale skin, rapid heartbeat, and dark urine. Patients with a deficiency in an enzyme called glucose-6-phosphate dehydrogenase (G6PD) are at a higher risk.
- Clostridium difficile-Associated Diarrhea: Antibiotics can alter the normal intestinal microbiome, leading to the overgrowth of C. diff bacteria. Infection may range from mild diarrhea to fatal colitis.
Who Should Avoid Nitrofurantoin?
According to drug manufacturing labels, the following people should not take nitrofurantoin:
- Significant renal impairment (creatinine clearance under 60 mL/min or significantly elevated serum creatinine)
- Anuria (urine output less than 100 mL/24 hours)
- Oliguria (urine output less than 400 mL/24 hours)
- Pregnant patients at term (38-42 weeks gestation), during labor and delivery, or when the onset of labor is imminent
- Neonates under one-month-old
- Medical history of liver dysfunction associated with nitrofurantoin
- Known allergy to nitrofurantoin
Drug Interactions and Precautions
Antibiotics should only be used to treat bacterial infections. They do not treat viral infections.
Macrobid is not indicated for treating complicated UTIs, including kidney infections, such as pyelonephritis or perinephric abscesses. If you begin to experience any of the following symptoms, call your doctor immediately:
- Fever and chills
- Back, side, or groin pain
- Nausea and vomiting
Nitrofurantoin can interact with other medications, increasing the risk of side effects or preventing the medicines from working well. Do not take nitrofurantoin with the following:
- Antacids (used to treat heartburn) containing magnesium trisilicate interfere with the body's ability to absorb nitrofurantoin, reducing its efficacy.
- Uricosuric drugs (used to lower uric acid levels in the blood), such as probenecid and sulfinpyrazone, interfere with how the body moves nitrofurantoin through the kidneys. This can cause higher levels of the drug in the blood, potentially increasing the risk of side effects. At the same time, because less nitrofurantoin is excreted in the urine, it may not be as effective at treating the UTI.
Alternative Treatments
When nitrofurantoin isn't the best treatment option, there are other options to consider for managing UTIs.
Other Antibiotics for UTIs
When choosing an antibiotic to treat an uncomplicated UTI, doctors consider several factors, including:
- Antibiotic efficacy
- Side effect profile
- Rates of bacterial resistance
- Cost and availability
- Patient allergies
When nitrofurantoin is contraindicated, alternative antimicrobial agents for managing acute, uncomplicated cystitis include:
- Fosfomycin
- Trimethoprim-sulfamethoxazole
- Ciprofloxacin
- Levofloxacin
- Ofloxacin
- Amoxicillin-clavulanate
- Cefdinir
- Cefpodoxime
Non-Antibiotic Approaches
Lifestyle habits help prevent UTIs:
- Urinate before and after sexual activity
- Wipe from front to back after having a bowel movement
- Change menstrual products, such as pads and tampons, regularly
- Avoid douching and applying deodorants on/in the vagina
- Stay well hydrated by drinking at least 1.5 liters of water daily
Certain over-the-counter supplements can also support a healthy urinary tract:
- According to a systematic review, daily probiotics, especially those containing Lactobacillus rhamnosus and reuteri, are associated with reduced UTI recurrence rates in women.
- Berberine is a plant-derived compound that has been shown to prevent bacterial (including E. coli) adhesion to human cells.
- Similarly, cranberry inhibits bacterial adhesion in the urinary tract, preventing bacterial growth and infection. According to a systematic review and meta-analysis, regular supplementation with cranberry reduced UTI incidence in at-risk populations.
FAQs About Nitrofurantoin
What Do I Do If I Miss a Dose?
If you miss a dose, take it as soon as you remember unless it is almost time for your next dose. In that case, skip the missed dose and resume your regular schedule. Do not double up on doses to make up for a missed one.
Can Nitrofurantoin Be Used Long-Term?
Nitrofurantoin may be prescribed for long-term, prophylactic use under close medical supervision in specific cases, such as the prevention of recurrent UTIs.
Is Nitrofurantoin Safe for Elderly Patients?
Elderly patients may be at higher risk for side effects, particularly those related to the lungs and liver. As such, nitrofurantoin should be used cautiously in older adults, and the dosage may need to be adjusted depending on kidney function.
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Key Takeaways
- Nitrofurantoin is an FDA-approved, first-line antibiotic for treating uncomplicated UTIs, especially those caused by E. coli bacteria.
- Nitrofurantoin is often the preferred antibiotic for UTIs due to its high concentration in the urine, favorable safety profile, and low rates of bacterial resistance.
- Its most common side effect includes gastrointestinal upset, which can often be prevented by taking the medication with food.
- More serious side effects are rare but can occur. Always tell a doctor if you experience symptoms like severe diarrhea, fatigue, numbness and tingling, jaundice, cough, and shortness of breath.
- If you cannot take nitrofurantoin, discuss alternative antibiotics and natural remedies with your doctor for treating and preventing UTIs.
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