When is nitrofurantoin (antibiotic) contraindicated?

From the Guidelines

Nitrofurantoin is contraindicated in patients with creatinine clearance less than 30 mL/min, during the third trimester of pregnancy, in infants under one month of age, and in those with known hypersensitivity, G6PD deficiency, or a history of nitrofurantoin-induced hepatotoxicity, pulmonary reactions, or peripheral neuropathy. The medication should be used with caution in patients with renal impairment, as it may accumulate in the bloodstream and increase the risk of toxicity 1. According to the most recent guidelines, nitrofurantoin is not recommended for use in children under 12 years of age, as it is not approved by the Taiwan FDA for this age group 1. Additionally, nitrofurantoin is not suitable for treating systemic infections or pyelonephritis, as it does not achieve adequate tissue concentrations outside the urinary tract 1. Some specific situations where nitrofurantoin is contraindicated include:

• Renal impairment with creatinine clearance less than 30 mL/min
• Third trimester of pregnancy (weeks 36-42)
• Infants under one month of age
• Known hypersensitivity to nitrofurantoin or any components of the formulation
• G6PD deficiency
• History of nitrofurantoin-induced hepatotoxicity, pulmonary reactions, or peripheral neuropathy It is essential to consider these contraindications when prescribing nitrofurantoin to ensure the safe and effective treatment of patients 1.

From the FDA Drug Label

ADVERSE REACTIONS: Respiratory: CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR. Hepatic: Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely Neurologic: Peripheral neuropathy, which may become severe or irreversible, has occurred Fatalities have been reported. Dermatologic: Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely. Allergic: A lupus-like syndrome associated with pulmonary reactions to nitrofurantoin has been reported Also, angioedema; maculopapular, erythematous, or eczematous eruptions; pruritus; urticaria; anaphylaxis; arthralgia; myalgia; drug fever; chills; and vasculitis (sometimes associated with pulmonary reactions) have been reported. Hematologic: Cyanosis secondary to methemoglobinemia has been reported rarely. Laboratory Adverse Events: The following laboratory adverse events have been reported with the use of nitrofurantoin: increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus, eosinophilia, glucose-6-phosphate dehydrogenase deficiency anemia (see WARNINGS), agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia In most cases, these hematologic abnormalities resolved following cessation of therapy. Aplastic anemia has been reported rarely.

Nitrofurantoin is contraindicated in:

• Pulmonary reactions: patients who have experienced previous pulmonary reactions to nitrofurantoin
• Hepatic reactions: patients with hepatic impairment or previous hepatic reactions to nitrofurantoin
• Neurologic reactions: patients with previous neurologic reactions, such as peripheral neuropathy
• Dermatologic reactions: patients with previous dermatologic reactions, such as exfoliative dermatitis or erythema multiforme
• Allergic reactions: patients with a history of allergic reactions to nitrofurantoin, including anaphylaxis
• Hematologic reactions: patients with glucose-6-phosphate dehydrogenase deficiency, as they are at risk of developing hemolytic anemia
• Renal impairment: patients with creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine 2

From the Research

Contraindications of Nitrofurantoin

• Nitrofurantoin is contraindicated in pregnant women at term and in neonates 3
• It is also contraindicated in patients with a known sensitivity to oxidant drugs, notably glucose-6-phosphate dehydrogenase (G6PD) deficiency, as it may cause haemolytic anaemia 3
• The contraindication of nitrofurantoin in patients with a creatinine clearance (CrCl) below 60 mL/min is not supported by strong evidence, and some studies suggest that it may be used in patients with a CrCl of 40 mL/min or higher 4 or even 30 mL/min or higher 5, 6

Renal Impairment and Nitrofurantoin Use

• The use of nitrofurantoin in patients with renal impairment is a topic of debate, with some studies suggesting that it may be safe and effective in patients with a CrCl of 30 mL/min or higher 5, 6
• However, concerns about increased risks of serious adverse reactions in patients with reduced renal function have limited the use of nitrofurantoin in this population 4

Special Populations

• In frail, community-dwelling, older adults with renal impairment, nitrofurantoin may be a viable treatment option for urinary tract infections, especially when other antibiotics are not suitable 5
• The American Geriatrics Society has updated its recommendations to allow for the use of nitrofurantoin in patients with a CrCl of 30 mL/min or higher, based on retrospective studies that identified its safety and efficacy in this population 6