Usage
Nitrofurantoin is a synthetic antibacterial agent primarily used for the treatment and prophylaxis of uncomplicated urinary tract infections (UTIs). It is effective against a range of gram-positive and gram-negative bacteria, including Escherichia coli, Staphylococcus saprophyticus, Enterococcus faecalis, Klebsiella pneumoniae, and Enterobacter species. Nitrofurantoin is classified as a nitrofuran antibiotic. Its mechanism of action involves inhibiting bacterial enzymes essential for carbohydrate metabolism, DNA synthesis, and cell wall formation.
Alternate Names
While “nitrofurantoin” is the generic name, brand names vary depending on the formulation and country. Some examples include Macrobid, Macrodantin, and Furadantin.
How It Works
Pharmacodynamics: Nitrofurantoin exerts its antibacterial effects primarily within the urinary tract due to its high concentration in urine. It disrupts several bacterial enzymatic processes, including those involved in carbohydrate metabolism, DNA synthesis, RNA synthesis, cell wall synthesis, and protein synthesis, ultimately leading to bacterial cell death.
Pharmacokinetics: Nitrofurantoin is administered orally and is well-absorbed from the gastrointestinal tract. Absorption is enhanced when taken with food. It is rapidly metabolized in the body, primarily in the liver, and excreted mainly in the urine, giving it its high urinary concentration. The macrocrystalline formulations (Macrodantin) are absorbed more slowly, leading to a longer duration of action. The monohydrate/macrocrystal formulation (Macrobid) has a dual release mechanism, resulting in both rapid and sustained release.
Mode of Action: Nitrofurantoin acts through multiple mechanisms. It inhibits bacterial enzymes involved in carbohydrate metabolism, disrupts DNA and RNA synthesis, and interferes with cell wall formation. These actions work synergistically to kill bacteria or inhibit their growth.
Elimination: Nitrofurantoin is primarily eliminated via renal excretion. A small amount is excreted in the bile and feces. Dosage adjustments are required for patients with renal impairment.
Dosage
Standard Dosage
Adults:
- Uncomplicated UTIs:
- Macrocrystals (Macrodantin): 50-100 mg four times daily for 7 days.
- Monohydrate/macrocrystals (Macrobid): 100 mg twice daily for 5-7 days.
- Prophylaxis: 50-100 mg at bedtime.
- Severe/Chronic UTIs: 100mg four times daily for 7 days
- Long-term suppression therapy: 50-100 mg once daily
Children (over 3 months):
- 5-7 mg/kg/day divided into four doses for 7 days.
- Suppressive therapy: 1mg/kg/day once daily
Special Cases:
- Elderly Patients: Use with caution. Start with a lower dose (e.g., 50 mg twice daily) and monitor for adverse effects. Dosage adjustments may be needed based on renal function.
- Patients with Renal Impairment: Contraindicated in patients with creatinine clearance <45 mL/min. Use with caution if creatinine clearance is between 30-44 mL/min for short courses (3-7 days) if benefits outweigh risks.
- Patients with Hepatic Dysfunction: Use with caution. Monitor liver function tests.
- Patients with Comorbid Conditions: Dosage adjustments may be necessary depending on the specific comorbidity.
Clinical Use Cases
Nitrofurantoin’s clinical use is primarily limited to uncomplicated UTIs. It is not recommended for use in the following settings due to poor tissue penetration or risk of inadequate therapeutic levels:
- Intubation
- Surgical Procedures (prophylactic usage for certain urological procedures may be an exception)
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Dose adjustments are based on creatinine clearance. For patients with mild to moderate renal impairment, a reduced dose and close monitoring are required.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Loss of appetite
- Diarrhea
- Headache
- Dizziness
- Drowsiness
- Rust-colored or brownish urine
Rare but Serious Side Effects:
- Allergic reactions (rash, hives, itching, swelling, difficulty breathing)
- Lung problems (cough, chest pain, shortness of breath)
- Liver damage (jaundice, dark urine, abdominal pain)
- Peripheral neuropathy (numbness, tingling, pain in hands and feet)
- Hemolytic anemia (fatigue, shortness of breath, pale skin)
Long-Term Effects:
- Pulmonary fibrosis (with prolonged use)
- Peripheral neuropathy (with prolonged use)
- Hepatitis (with prolonged use)
Adverse Drug Reactions (ADR):
- Angioedema
- Cyanosis
- Hepatitis
- Pulmonary reactions
- Peripheral neuropathy
- Hemolytic anemia
Contraindications
- Hypersensitivity to nitrofurantoin
- Anuria, oliguria, or severe renal impairment (CrCl < 45 mL/min)
- Pregnancy at term (38-42 weeks), during labor and delivery
- Infants younger than 1 month
- G6PD deficiency
Drug Interactions
- Antacids containing magnesium trisilicate: Reduced absorption of nitrofurantoin.
- Probenecid and sulfinpyrazone: Increased blood levels of nitrofurantoin.
- Oral typhoid vaccine: Decreased efficacy of the vaccine.
- Methotrexate: Increased methotrexate toxicity.
- Other antibiotics: Potential antagonistic effects.
- Food: Taking nitrofurantoin with food improves absorption and tolerance.
Pregnancy and Breastfeeding
- Pregnancy: Generally safe during the first and second trimesters. Contraindicated at term (38-42 weeks) due to risk of neonatal hemolytic anemia.
- Breastfeeding: Small amounts are excreted in breast milk. Can be used during breastfeeding but use with caution especially during the first month and with hyperbilirubinemic infants due to the risk of hemolytic anemia. Monitor the infant for jaundice and hemolytic anemia.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial enzymes crucial for carbohydrate metabolism, DNA, RNA, cell wall, and protein synthesis.
- Side Effects: Nausea, vomiting, loss of appetite, headache, dizziness, peripheral neuropathy, lung toxicity, liver damage, hemolytic anemia.
- Contraindications: Hypersensitivity, anuria/oliguria, severe renal impairment, pregnancy at term, infants <1 month, G6PD deficiency.
- Drug Interactions: Antacids, probenecid, sulfinpyrazone, oral typhoid vaccine, methotrexate.
- Pregnancy & Breastfeeding: Generally safe in early pregnancy, contraindicated at term; use cautiously when breastfeeding.
- Dosage: Adults: 50-100 mg four times daily or 100 mg twice daily; Children: 5-7 mg/kg/day divided into four doses.
- Monitoring Parameters: Renal function, liver function, complete blood count, signs of pulmonary or hepatic toxicity, blood glucose, observe for development of peripheral neuropathy.
Popular Combinations
Nitrofurantoin is not typically used in combination with other antibiotics.
Precautions
- Monitor renal and liver function, especially during long-term therapy.
- Discontinue use if signs of pulmonary or hepatic toxicity occur.
- Monitor blood glucose levels in patients with diabetes
- Alert for signs and symptoms of peripheral neuropathy
- Advise patients to take with food to enhance absorption and reduce gastrointestinal upset
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nitrofurantoin?
A: Adults: 50-100 mg four times daily or 100 mg twice daily for 5-7 days; Children: 5-7 mg/kg/day divided into four doses for 7 days. Prophylaxis: 50-100 mg at bedtime. Adjustments are needed for renal impairment.
Q2: What are the common side effects of Nitrofurantoin?
A: Nausea, vomiting, loss of appetite, diarrhea, headache, dizziness, drowsiness, and rust-colored urine are common side effects.
Q3: Is Nitrofurantoin safe during pregnancy?
A: Generally safe during the first and second trimesters. Contraindicated in the third trimester and during labor and delivery.
Q4: Can Nitrofurantoin be used in patients with renal impairment?
A: Contraindicated with creatinine clearance < 45 mL/min. Use cautiously if creatinine clearance is between 30 and 44 mL/min, and only for short term treatment for uncomplicated lower UTIs.
Q5: How should Nitrofurantoin be administered?
A: Orally, with food to enhance absorption and tolerance.
Q6: What are the most serious side effects of Nitrofurantoin?
A: Pulmonary reactions, hepatitis, peripheral neuropathy, hemolytic anemia, and allergic reactions.
Q7: What should be done if a patient develops a pulmonary reaction to nitrofurantoin?
A: Discontinue the medication immediately and initiate appropriate respiratory support if necessary. Corticosteroids may be considered.
Q8: Can nitrofurantoin be used to treat pyelonephritis?
A: No, nitrofurantoin does not achieve adequate concentrations in the kidney tissue to effectively treat pyelonephritis.
Q9: Does nitrofurantoin interact with other medications?
A: Yes, significant interactions exist with antacids containing magnesium trisilicate, probenecid, sulfinpyrazone, and oral typhoid vaccine. It can also interact with Methotrexate.
