Nitrofurantoin

1. Health Canada Product Monograph — Nitrofurantoin

• Nitrofurantoin treats urinary tract infections, including cystitis, pyelitis, and pyelonephritis, caused by susceptible bacteria.
• It is not effective for infections outside the urinary tract, such as renal cortical or perinephric abscesses or prostatitis, because it does not reach adequate tissue concentrations there.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Nitrofurantoin's safety in pregnancy has not been firmly established and it should only be used if the expected benefit outweighs the possible risk.
• It must not be used at term (during labour and delivery) because of the risk of hemolytic anemia in the newborn from immature red blood cell enzyme systems.
• Discuss the risks and benefits with a healthcare provider before using nitrofurantoin earlier in pregnancy for a resistant infection.

• Nitrofurantoin's safety during breastfeeding has not been established, and it should be used with caution while nursing, particularly if the infant is under 1 month old or has glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• Older adults may respond differently to nitrofurantoin, and age-related decline in kidney function increases the risk of drug accumulation and toxicity, so kidney function should be checked before starting therapy.

• Nitrofurantoin has not been established as safe or effective in infants under 1 month of age and is not authorized for use in this age group.

• The usual adult dose of nitrofurantoin is 50 mg to 100 mg four times a day.
• Treatment should continue for at least 1 week and for at least 3 days after the urine tests free of bacteria; if the infection persists, the patient should be reassessed.
• For long-term suppressive therapy, a lower maintenance dose may be considered.
• Nitrofurantoin should not be used in patients with significant kidney impairment (creatinine clearance under 40 mL/min), since reduced clearance both raises toxicity risk and lowers effectiveness.
• If a dose is missed, take it as soon as remembered, unless it is almost time for the next dose, in which case the missed dose should be skipped rather than doubled.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Reported cases of nitrofurantoin overdose have generally caused only vomiting, without other specific symptoms.
• If vomiting does not occur soon after a significant overdose, inducing vomiting may be recommended.
• There is no specific antidote; maintaining a high fluid intake helps promote urinary excretion of the drug after an overdose.

• Nausea and vomiting are the most frequently reported side effects.
• Loss of appetite may occur.
• Diarrhea or abdominal pain may occur.
• Headache may occur.
• Dizziness may occur.
• Drowsiness may occur.
• Joint pain (arthralgia) may occur.
• Fever and chills may occur.
• Temporary hair thinning or loss has been reported.
• Skin rash or itching may occur.
• Rapid, uncontrolled eye movements (nystagmus) have been reported.
• Nitrofurantoin can turn the urine a rust-yellow to brown colour, which is harmless.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Hemolytic anemia can occur, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; any sign of hemolysis should prompt immediate discontinuation.
• Peripheral neuropathy (numbness, tingling, or pain in the hands or feet) may develop and can become severe or irreversible, especially in patients with kidney impairment, anemia, diabetes, vitamin B deficiency, or debilitating illness.
• Acute or chronic pulmonary reactions can occur, ranging from fever, chills, cough, and chest pain with acute onset in the first week of treatment, to a slower-developing pattern of breathlessness and lung scarring (interstitial pneumonitis or fibrosis) with prolonged use.
• Liver injury, including cholestatic jaundice and, rarely, hepatitis, may occur and is more likely with higher doses, especially in women.
• Serious allergic reactions, including anaphylaxis and asthma attacks in patients with a history of asthma, can occur.
• Blood disorders such as granulocytopenia, eosinophilia, and megaloblastic anemia have been reported.
• Drug-induced fever typically develops after seven to ten days of treatment and resolves within about 48 hours of stopping the drug.
• Angioedema, with swelling of the face, lips, tongue, or throat, may occur.
• Superinfection with resistant organisms, limited to the urinary tract, may occur with prolonged use.
• Seek immediate medical attention for signs of severe allergic reaction, breathing difficulty, unusual bruising or bleeding, yellowing of the skin or eyes, or numbness and tingling in the hands or feet.

• Use with caution in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, due to the risk of hemolytic anemia.
• Use with caution in patients with any degree of kidney impairment, and avoid use if creatinine clearance is below 40 mL/min.
• Use with caution in older adults, who are more likely to have reduced kidney function and to experience pulmonary or hepatic side effects.
• Use with caution in patients with diabetes, anemia, vitamin B deficiency, or debilitating disease, which increase the risk of peripheral neuropathy.
• Use with caution in patients with lung, liver, or nervous system disease.
• Use with caution in patients with a history of asthma, due to increased risk of allergic or asthmatic reactions.
• Nitrofurantoin may cause dizziness or drowsiness; caution patients about driving or operating machinery until they know how it affects them.
• This medication contains lactose and should be used with caution in patients with rare hereditary lactose intolerance.
• Use with caution in patients who are pregnant, planning pregnancy, or breastfeeding.

• Contraindicated in patients with known hypersensitivity to nitrofurantoin or any ingredient in the formulation.
• Contraindicated in patients with anuria, oliguria, or significant kidney impairment (creatinine clearance under 40 mL/min).
• Contraindicated in pregnant patients at term, due to the risk of hemolytic anemia in the newborn.
• Contraindicated in infants under 1 month of age, for the same reason.

• Nitrofurantoin should not be given together with other drugs that can impair kidney function, since this increases the risk of toxicity.
• Magnesium trisilicate antacids can reduce the absorption and effectiveness of nitrofurantoin if taken at the same time.
• Probenecid and sulfinpyrazone can reduce the urinary excretion of nitrofurantoin, lowering its effectiveness against urinary infection while increasing the risk of systemic toxicity.
• Concurrent use with fluoroquinolone antibiotics may reduce the antibacterial effectiveness of both drugs and is generally avoided.

• Nitrofurantoin must be taken with food or milk, which improves absorption and helps reduce stomach upset.

• Take nitrofurantoin with meals or a glass of milk, spaced evenly through the day to match the four-times-daily schedule.

• Store at room temperature, below 25°C, and protect from light.

• Nitrofurantoin is an antibiotic for urinary tract infections; take the full course with food, even if symptoms improve early, and contact your pharmacist or doctor promptly if you develop numbness or tingling, yellowing of the skin, or breathing problems.