Indications : התוויות

1. Therapeutic indications
Treatment of acute uncomplicated urinary tract infections (acute cystitis) caused by susceptible strains of Escherichia coli or Staphylococcus Saprophyticus in adult and adolescence 12 years and older.
Nitrofurantoin is not indicated for the treatment of pyelonephritis or perinephric abscesses.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Macrobid and other antibacterial drugs, Macrobid should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Pharmacotherapeutic group: Antibacterials for systemic use, nitrofuran derivatives.
ATC code: J01XE01

2. DESCRIPTION
Nitrofurantoin is an antibacterial agent specific for urinary tract infections. Macrobid (Nitrofurantoin Capsules, USP) (monohydrate/macrocrystals) is a hard gelatin capsule.
Each capsule contains 100 mg of nitrofurantoin in the form of 25 mg of nitrofurantoin macrocrystals and 75 mg of nitrofurantoin monohydrate.
The chemical name of nitrofurantoin macrocrystals is 1-[[[5-nitro-2- furanyl]methylene]amino]-2,4-imidazolidinedione. The chemical structure is the following:


Molecular Weight: 238.16
The chemical name of nitrofurantoin monohydrate is 1-[[[5-nitro-2- furanyl]methylene]amino]-2,4- imidazolidinedione monohydrate. The chemical structure is the following:

Molecular Weight: 256.17
Inactive Ingredients: Each capsule contains lactose monohydrate, gelatin, povidone, corn starch, compressible sugar, talc, carbomer 934P, magnesium stearate, titanium dioxide, D&C Ye low No. 10, FD&C Red No. 40, FD&C Blue No. 1, gray ink, purified water.
Meets USP Dissolution Test 8.

3. CLINICAL PHARMACOLOGY
Each Macrobid capsule contains two forms of nitrofurantoin. Twenty-five percent is macrocrystaline nitrofurantoin, which has slower dissolution and absorption than 
nitrofurantoin monohydrate. The remaining 75% is nitrofurantoin monohydrate contained in a powder blend which, upon exposure to gastric and intestinal fluids, forms a gel matrix that releases nitrofurantoin over time. Based on urinary pharmacokinetic data, the extent and rate of urinary excretion of nitrofurantoin from the 100 mg Macrobid capsule are similar to those of 50 mg or 100 mg Macrodantin (nitrofurantoin macrocrystals) capsule.
Approximately 20% to 25% of a single dose of nitrofurantoin is recovered from the urine unchanged over 24 hours.
Plasma nitrofurantoin concentrations after a single oral dose of the 100 mg nitrofurantoin capsule are low, with peak levels usually less than 1 mcg/mL. Nitrofurantoin is highly soluble in urine, to which it may impart a brown color. When nitrofurantoin is administered with food, the bioavailability of nitrofurantoin is increased by approximately      40%.

4. MICROBIOLOGY
Nitrofurantoin is a nitrofuran antimicrobial agent with activity against certain Gram- positive and Gram-negative bacteria.

4.1 Mechanism of Action
The mechanism of the antimicrobial action of nitrofurantoin is unusual among antibacterials.
Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other macromolecules. As a result of such inactivations, the vital biochemical processes of protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited.
Nitrofurantoin is bactericidal in urine at therapeutic doses. The broad-based nature of this mode of action may explain the lack of acquired bacterial resistance to nitrofurantoin, as the necessary multiple and simultaneous mutations of the target macromolecules would likely be lethal to the bacteria.