Elephant specific information, if available, is in blue.

Chemistry – A synthetic, nitrofuran antibacterial, nitrofurantoin occurs as a bitter tasting, lemon-yellow, crystalline powder with a pKa of 7.2. It is very slightly soluble in water or alcohol.

Storage/Stability/Compatibility – Nitrofurantoin preparations should be stored in tight containers at room temperature and protected from light. The oral suspension should not be frozen. Nitrofurantoin will decompose if contacted with metals other than aluminum or stainless steel.

Pharmacology – Nitrofurantoin acts usually as a bacteriostatic antimicrobial, but may be bactericidal depending on the concentration of the drug and the susceptibility of the organ­ism. The exact mechanism of action of nitrofurantoin has not been fully elucidated, but the drug apparently inhibits various bacterial enzyme systems, including acetyl coenzyme A. Nitrofurantoin has greater antibacterial activity in acidic environments.

Nitrofurantoin has activity against several gram negative and some gram positive organ­isms, including many strains of E. coli, Klebsiella, Enterobacter, Enterococci, Staphylococcus aureus and epidermidis, Enterobacter, Citrobacter, Salmonella, Shigella, and Corynebacterium. It has little or no activity against most strains of Proteus, Serratia orAcinetobacter and has no activity against Pseudomonas sp..

Uses/Indications – Considered a urinary tract antiseptic, nitrofurantoin is used primarily in small animals, but also occasionally in horses in the treatment of lower urinary tract infec­tions caused by susceptible bacteria. It is not effective in treating renal cortical or per­inephric abscesses or other systemic infections.

Pharmacokinetics – Nitrofurantoin is rapidly absorbed from the GI tract and the presence of food may enhance the absorption of the drug. Macrocrystalline forms of the drug may be absorbed more slowly with less GI upset. Because of its slower absorption, urine levels of the drug may be prolonged.

Because of the rapid elimination of the drug after absorption, therapeutic levels in the systemic circulation are not maintained. Approximately 20-60% of the drug is bound to serum proteins. Peak urine levels occur within 30 minutes of dosing. The drug crosses the placenta and only minimal quantities of the drug are found in milk.

Approximately 40-50% of the drug is eliminated into urine unchanged via both glomeru­lar filtration and tubular secretion. Some of the drug is metabolized, primarily in the liver. Elimination half-lives in humans with normal renal function average 20 minutes.

Contraindications/Precautions/Reproductive Safety – Nitrofurantoin is contraindicated in patients with renal impairment as the drug is much less efficacious and the development of toxicity is much more likely. The drug is also contraindicated in patients hypersensitive to it.

In humans, the drug is contraindicated in pregnant patients at term and in neonates as hemolytic anemia can occur secondary to immature enzyme systems. Safe use of the drug during earlier stages of pregnancy has not been determined. Nitrofurantoin has been impli­cated in causing infertility in male dogs. Use only when the benefits of therapy outweigh the potential risks.

Adverse Effects/Warnings – In dogs and cats, gastrointestinal disturbances and hepatopa­thy can occur with this drug. Neuropathies, chronic active hepatitis, hemolytic anemia and pneumonitis have been described in humans, but are believed to occur very rarely in ani­mals.

Overdosage/Acute Toxicity – No specific information was located. Because the drug is rapidly absorbed and excreted. Patients with normal renal function should require little therapy when mild overdoses occur. Massive overdoses should be handled by emptying the gut using standard protocols if the ingestion was relatively recent, and then monitoring the patient for adverse effects (see above).

Drug Interactions – The uricosuric agents sulfinpyrazone or probenecid may inhibit the renal excretion of nitrofurantoin and potentially increase its toxicity and reduce its effec­tiveness in urinary tract infections. Nitrofurantoin may antagonize the antimicrobial activity of the fluoroquinolones (e.g., enrofloxacin, ciprofloxacin) and their concomitant use is not recommended. Magnesium trisilicate containing antacids may inhibit the oral absorption of nitrofuran­toin. Food or anticholinergic drugs may increase the oral bioavailability of nitrofurantoin.

Drug/Laboratory Interactions – Nitrofurantoin may cause false-positive urine glucose determinations if using cupric sulfate solutions (Benedict’s reagent, Clinitest®). Tests us­ing glucose oxidase methods (Tes-Tape®, Clinistix®) are not affected by nitrofurantoin.

Nitrofurantoin may cause decreases in blood glucose, and increases in serum creatinine, bilirubin and alkaline phosphatase.

Doses –

Horses:

For susceptible urinary tract infections:

a)   2.5 – 4.5 mg/kg PO tid (Robinson 1987)

b)   10 mg/kg PO daily (Huber 1988a)

Monitoring Parameters –

1)   Clinical efficacy

2)   Adverse effects

3)   Periodic liver function tests should be considered with chronic therapy

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

Veterinary-Approved Products: None

Human-Approved Products:

Nitrofurantoin Macrocrystals Capsules 25 mg, 50 mg, and 100 mg; Macrodantin®   (Procter & Gamble Pharm); Macrobid® (Procter & Gamble Pharm); generic; (Rx)

Nitrofurantoin Oral Suspension 5 mg/ml in 60 ml and pint bottles; Furadantin® (Dura); (Rx)