nitrofurantoin macrocrystals
Apo-Nitrofurantoin ◆, Novo-Furantoin ◆, Macrobid, Macrodantin

nitrofurantoin microcrystals
Furadantin

Available forms
Available by prescription only
macrocrystals
Capsules: 25 mg, 50 mg, 100 mg
Capsules (dual-release): 100 mg
microcrystals
Suspension: 25 mg/5 ml

Indications and dosages
 Initial or recurrent urinary tract infections caused by susceptible organisms. Adults and children older than age 12: 50 to 100 mg P.O. q.i.d. or 100 mg dual-release capsules q 12 hours for 7 days.
Children ages 1 month to 12 years: 5 to 7 mg/kg/24 hours P.O. daily, divided q.i.d.
 Long-term suppression therapy. Adults: 50 to 100 mg P.O. daily h.s. as a single dose.
Children: As low as 1 mg/kg daily P.O. in a single dose or two divided doses.

Pharmacodynamics
Antibacterial action: Nitrofurantoin has bacteriostatic action at low levels and possible bactericidal action at high levels. Although its exact mechanism of action is unknown, it may inhibit bacterial enzyme systems, interfering with bacterial carbohydrate metabolism. Drug is most active at an acidic pH.
Spectrum of activity includes many common gram-positive and gram-negative urinary pathogens, including Escherichia coli, Staphylococcus aureus, enterococci, and certain strains of Klebsiella and Enterobacter sp. Organisms that usually resist nitrofurantoin include Acinetobacter, Proteus, Providencia, Pseudomonas, and Serratia sp.

Pharmacokinetics
Absorption: When administered orally, drug is well absorbed (mainly by the small intestine) from GI tract. Presence of food aids dissolution of drug and speeds absorption. The macrocrystal form exhibits slower dissolution and absorption; it causes less GI distress.
Distribution: Crosses into bile and placenta. 60% binds to plasma proteins. Plasma half-life is about 20 minutes. Urine levels peak in about 30 minutes when drug is given as microcrystals, somewhat later when given as macrocrystals.
Metabolism: Metabolized partially in the liver.
Excretion: About 30% to 50% of dose is eliminated by glomerular filtration and tubular secretion into urine as unchanged drug within 24 hours. Some drug may appear in breast milk.

Contraindications and precautions
Contraindicated in patients who are hypersensitive to drug or its components and in pregnant women at term (38 to 42 weeks’ gestation). Also contraindicated during labor and delivery and when the onset of labor is imminent. Contraindicated in children age 1 month and younger and in patients with moderate to severe renal impairment, anuria, oliguria, or creatinine clearance less than 60 ml/minute.
  Use cautiously in patients with impaired renal function, anemia, diabetes mellitus, electrolyte abnormalities, vitamin B deficiency, debilitating disease, or G6PD deficiency.

Interactions
Drug-drug. Magnesium trisilicate antacids: May decrease nitrofurantoin absorption. Separate administration times.
Probenecid, sulfinpyrazone: Reduces renal excretion of nitrofurantoin. Monitor patient for increased toxicity and decreased clinical effect.
Quinolone derivatives, such as cinoxacin, ciprofloxacin, nalidixic acid, and norfloxacin: May antagonize anti-infective effects. Monitor patient for decreased clinical effect.
Drug-food. Food: Enhances bioavailability of nitrofurantoin. Give drug with food.

Adverse reactions
CNS: peripheral neuropathy, headache, dizziness, drowsiness, ascending polyneuropathy (with high doses or renal impairment).
GI: anorexia, nausea, vomiting, abdominal pain, diarrhea.
GU: overgrowth of nonsusceptible organisms in the urinary tract.
Hematologic: hemolysis in patients with G6PD deficiency (reversed after stopping drug), agranulocytosis, thrombocytopenia.
Hepatic: hepatitis, hepatic necrosis.
Respiratory: pulmonary sensitivity reactions (cough, chest pain, fever, chills, dyspnea, pulmonary infiltration with consolidation or pleural effusion), asthmatic attacks in patients with history of asthma.
Skin: maculopapular, erythematous, or eczematous eruption; pruritus; urticaria; exfoliative dermatitis;Stevens-Johnson syndrome, transient alopecia.
Other: hypersensitivity reactions (anaphylaxis), drug fever.

Effects on lab test results
• May increase bilirubin and alkaline phosphatase levels. May decrease glucose level.
• May decrease granulocyte and platelet counts.

Overdose and treatment
Acute overdose may result in nausea and vomiting.
 Treat symptomatically. No specific antidote is known. Increase fluid intake to promote urinary excretion of drug. Nitrofurantoin is dialyzable.

Special considerations
• Obtain culture and sensitivity test results before starting therapy, and repeat as needed.
• Oral suspension may be mixed with water, milk, fruit juice, or formulas.
• Drug may turn urine brown or rust-yellow.
• Continue treatment for at least 3 days after sterile urine specimens have been obtained.
• Long-term therapy may cause overgrowth of nonsusceptible organisms, especially Pseudomonas sp.
• Monitor CBC regularly.
• Monitor fluid intake and output and pulmonary status.
• Nitrofurantoin may cause false-positive results in urine glucose tests using cupric sulfate reagents (such as Benedict’s test, Fehling’s solution, or Clinitest) because it reacts with these reagents.
Breast-feeding patients
• Safety hasn’t been established. Although drug appears in low levels in breast milk, no adverse reactions have been reported except in infants with G6PD deficiency, in whom hemolytic anemia may develop.
Pediatric patients
• Contraindicated in infants age 1 month and younger because their immature enzyme systems increase the risk of hemolytic anemia.

Patient education
• Instruct patient to take drug with food or milk to minimize GI distress. Have patient report any unpleasant side effects.
• Instruct patient to swallow capsule whole.
• Caution patient that drug may cause false-positive results in urine glucose tests using cupric sulfate reduction method (Clinitest) but not in glucose oxidase test (glucose enzymatic test strip, Diastix, or Chemstrip uG).
• Emphasize that bedtime dose is important because drug will remain in bladder longer.
• Warn patient that drug may turn urine brown or rust-yellow.
• Advise patient to protect drug from light and store in tightly closed container.
• Tell patient to complete full course of therapy to prevent reinfection.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use