Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

NITROFURANTOIN

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

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 exactmechanism of action of nitrofurantoin has not been fully elucidated, but the drug apparently inhibitsvarious bacterial enzyme systems, including acetyl coenzyme A. Nitrofurantoin has greaterantibacterial 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 aureusand epidermidis, Enterobacter, Citrobacter, Salmonella, Shigella, and Corynebacterium. It has littleor no activity against most strains of Proteus, Serratia or Acinetobacter and has no activity against
Pseudomonas sp..

Uses, Indications

Considered a urinary tract antiseptic, nitrofurantoin is used primarily in smallanimals, but also occasionally in horses in the treatment of lower urinary tract infections caused bysusceptible bacteria. It is not effective in treating renal cortical or perinephric abscesses or othersystemic infections.

Pharmacokinetics - NITROFURANTOIN

Nitrofurantoin is rapidly absorbed from the GI tract and the presence of foodmay enhance the absorption of the drug. Macrocrystalline forms of the drug may be absorbed moreslowly with less GI upset. Because of its slower absorption, urine levels of the drug may beprolonged.
Because of the rapid elimination of the drug after absorption, therapeutic levels in the systemiccirculation are not maintained. Approximately 20-60% of the drug is bound to serum proteins. Peakurine levels occur within 30 minutes of dosing. The drug crosses the placenta and only minimalquantities 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. Eliminationhalf-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 ismuch 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 hemolyticanemia can occur secondary to immature enzyme systems. Safe use of the drug during earlierstages 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 canoccur with this drug. Neuropathies, chronic active hepatitis, hemolytic anemia and pneumonitis havebeen described in humans, but are believed to occur very rarely in animals.

Overdosage, Acute Toxicity

No specific information was located. Because the drug is rapidlyabsorbed and excreted. Patients with normal renal function should require little therapy when mildoverdoses occur. Massive overdoses should be handled by emptying the gut using standardprotocols 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 renalexcretion 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 glucoseoxidase 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.
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