Nitrofurantoin

Urinary Tract Infections

Nitrofurantoin is primarily prescribed to treat acute, uncomplicated urinary tract infections, such as cystitis (bladder infection). It works by stopping the growth of specific types of bacteria in the urine that cause these infections.

Prevention of Infections

In some cases, healthcare providers prescribe nitrofurantoin for long-term use to prevent urinary tract infections from returning in individuals who experience them frequently.

Limitations of Use

This medication is specifically designed to concentrate in the urine, which makes it effective for bladder infections but less effective for other types of infections. It is generally not used for:

• Kidney infections (pyelonephritis).
• Infections located in tissues outside of the urinary tract.
• Prostatitis (infection of the prostate).

Nitrofurantoin is only effective against bacterial infections and will not work for viral infections, such as the common cold or flu.

How Nitrofurantoin Works

Nitrofurantoin is an antibacterial medication used specifically to treat urinary tract infections. Once the drug enters the body, it is quickly filtered by the kidneys and concentrated in the urine. This allows the medication to come into direct contact with the bacteria causing the infection.

Inside the bacterial cells, nitrofurantoin is converted into highly reactive substances by the bacteria's own enzymes. These substances attack several different parts of the bacteria at the same time, including:

• Genetic Material: It interferes with the DNA and RNA the bacteria need to function and reproduce.
• Protein Production: It disrupts the creation of essential proteins.
• Metabolism: It interferes with the bacteria's ability to process energy.
• Cell Wall: It damages the protective outer layer of the bacteria.

By attacking multiple targets simultaneously, nitrofurantoin effectively kills the bacteria or prevents them from multiplying. This complex mechanism of action also makes it more difficult for bacteria to develop resistance to the drug compared to some other antibiotics that only target one specific part of the cell.

Because the body clears nitrofurantoin from the bloodstream very quickly and sends it to the bladder, it does not reach high enough levels in the blood or other tissues to treat infections outside of the urinary tract.

Common Side Effects

• Nausea or vomiting
• Loss of appetite
• Stomach pain
• Diarrhea
• Dizziness or drowsiness
• Headache
• Rust-colored or brownish urine (this is a harmless side effect)

Serious Side Effects

Seek medical attention immediately if you experience any of the following serious symptoms:

• Lung reactions: Shortness of breath, chest pain, new or worsening cough, fever, or chills. These symptoms may occur shortly after starting the drug or after long-term use.
• Liver issues: Yellowing of the skin or eyes (jaundice), dark urine, pale stools, or pain in the upper right stomach area.
• Nerve damage: Numbness, tingling, or burning sensations in the hands or feet.
• Severe intestinal conditions: Persistent watery or bloody diarrhea, which may be accompanied by stomach cramps and fever.
• Allergic reactions: Skin rash, itching, hives, or swelling of the face, lips, or throat.
• Blood cell changes: Unusual bruising or bleeding, pale skin, or excessive tiredness.

Pulmonary Reactions

Nitrofurantoin can cause serious lung problems. Acute reactions may include fever, chills, cough, chest pain, and shortness of breath, usually appearing within the first week of treatment. Chronic reactions, such as interstitial pneumonitis or pulmonary fibrosis, can develop insidiously during long-term therapy and may result in permanent lung damage.

Hepatotoxicity

Serious liver reactions, including hepatitis, cholestatic jaundice, and hepatic necrosis, have occurred. Some cases have resulted in death. Monitoring liver function is often necessary during extended treatment, and the drug should be stopped immediately if liver injury is suspected.

Neuropathy

Peripheral neuropathy, which is nerve damage that may cause tingling or numbness, can occur and may become permanent. This risk is increased in those with kidney disease, diabetes, vitamin B deficiency, or electrolyte imbalances.

Hemolytic Anemia

This medication may cause the breakdown of red blood cells, especially in individuals with a glucose-6-phosphate dehydrogenase (G6PD) deficiency. If anemia occurs, the drug must be discontinued immediately.

Contraindications

• Kidney Disease: It should not be used by people with significant renal impairment or those who are not producing enough urine.
• Pregnancy and Neonates: It is contraindicated in pregnant patients at term (38 to 42 weeks) and in infants under one month of age due to the risk of hemolytic anemia.
• Previous Liver Issues: It should not be used by anyone with a history of liver dysfunction associated with previous nitrofurantoin use.

Diarrhea

Clostridioides difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including nitrofurantoin, and can range from mild diarrhea to fatal inflammation of the colon.

Pregnancy

Nitrofurantoin is frequently used for the treatment of urinary tract infections during pregnancy. However, its use is strictly contraindicated in patients at term (38 to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. This restriction exists because the drug may cause hemolytic anemia in the newborn. This condition occurs because the infant's red blood cell enzyme systems are not yet mature enough to handle the medication.

Breastfeeding

Nitrofurantoin is excreted in human breast milk in very small amounts. While it is generally considered compatible with breastfeeding for healthy, full-term infants, there are important exceptions:

• The medication should be avoided if the nursing infant has a known or suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• It should be used with caution when breastfeeding infants under one month of age due to the risk of hemolytic anemia.

Patients should discuss the potential benefits and risks with their healthcare provider before using nitrofurantoin while pregnant or breastfeeding.

Available Forms

Nitrofurantoin is administered by mouth and is available in the following forms:

• Capsules (Macrocrystals): This formulation contains larger crystals of the medication, which are absorbed at a specific rate in the digestive tract.
• Capsules (Monohydrate/Macrocrystals): This is a dual-release formulation that combines two forms of the drug to allow for slower absorption over a longer period.
• Oral Suspension: This is a liquid form of the medication, often used for patients who have difficulty swallowing capsules or when specific volume adjustments are necessary.

FDA Approval and Indications

Nitrofurantoin is an FDA-approved antibacterial agent indicated for the treatment of acute uncomplicated urinary tract infections (cystitis) caused by susceptible strains of Escherichia coli, Enterococci, Staphylococcus aureus, and certain strains of Klebsiella and Enterobacter species. It is also approved for the prevention of urinary tract infections in patients prone to recurrence.

Contraindications and Safety Warnings

The FDA has established several contraindications for nitrofurantoin use:

• Renal Impairment: It is contraindicated in patients with significant impairment of renal function (anuria, oliguria, or clinically significant creatinine clearance reduction) because of the risk of drug toxicity and lack of efficacy in the urine.
• Pregnancy and Neonates: Use is contraindicated in pregnant patients at term (38 to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. It is also contraindicated in neonates under one month of age due to the risk of hemolytic anemia.

Regulatory labeling also includes warnings regarding serious adverse reactions, such as pulmonary toxicity, which can occur acutely or chronically. Long-term therapy requires monitoring for potential liver injury (hepatotoxicity) and nerve damage (peripheral neuropathy). Nitrofurantoin is not a fluoroquinolone and is not subject to the specific FDA safety communications regarding aortic ruptures associated with that class of antibiotics.

Pregnancy Safety

Nitrofurantoin is commonly used to treat urinary tract infections during pregnancy. It is generally considered safe for use during the first and second trimesters when prescribed by a healthcare provider.

Late Pregnancy Warning

Nitrofurantoin should not be used during the final weeks of pregnancy (from 38 to 42 weeks gestation) or during labor and delivery. Using the medication at this stage can cause serious health issues for the newborn.

Risks to the Newborn

The restriction during late pregnancy is due to the risk of hemolytic anemia in the infant. Because a newborn's red blood cell enzyme systems are not fully developed at birth, exposure to nitrofurantoin just before or during delivery can cause the baby's red blood cells to break down prematurely.

If you are pregnant or planning to become pregnant, notify your doctor before taking this medication to ensure it is appropriate for your stage of pregnancy.