Nitrofurantoin Capsules

Name: Nitrofurantoin Capsules

Uses of Nitrofurantoin Capsules

  • It is used to treat or prevent a bladder infection.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Change in eyesight.
  • Eye pain.
  • Not able to control eye movements.
  • Feeling confused.
  • Very bad headache.
  • Low mood (depression).
  • Change in color of skin to a bluish color like on the lips, nail beds, fingers, or toes.
  • Feeling very tired or weak.
  • It is common to have diarrhea when taking this medicine. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking this medicine (nitrofurantoin capsules) or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

Description

Nitrofurantoin is an antibacterial agent specific for urinary tract infections. The nitrofurantoin monohydrate/macrocrystals capsules brand of nitrofurantoin is a hard gelatin capsule shell containing the equivalent of 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 carbomer 934P, corn starch, compressible sugar, D&C Yellow No. 10, edible gray ink, FD&C Blue No. 1, FD&C Red No. 40, gelatin, lactose, magnesium stearate, povidone, talc, and titanium dioxide.

Clinical pharmacology

Each nitrofurantoin monohydrate/macrocrystals capsule contains two forms of nitrofurantoin. Twenty-five percent is macrocrystalline 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 nitrofurantoin monohydrate/macrocrystals capsule are similar to those of the 50 mg or 100 mg nitrofurantoin macrocrystals capsule. Approximately 20-25% 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 monohydrate/macrocrystals capsules 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 monohydrate/macrocrystals capsules are administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%.

MICROBIOLOGY

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

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.

Interactions with Other Antibiotics

Antagonism has been demonstrated in vitro between nitrofurantoin and quinolone antimicrobials. The clinical significance of this finding is unknown.

Development of Resistance

Development of resistance to nitrofurantoin has not been a significant problem since its introduction in 1953. Cross-resistance with antibiotics and sulfonamides has not been observed, and transferable resistance is, at most, a very rare phenomenon.

Nitrofurantoin has been shown to be active against most strains of the following bacteria both in vitro and in clinical infections [see Indications and Usage].

Aerobic and facultative Gram-positive microorganisms:

Staphylococcus saprophyticus

Aerobic and facultative Gram-negative microorganisms:

Escherichia coli

At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for nitrofurantoin.  However, the efficacy of nitrofurantoin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled trials.

Aerobic and facultative Gram-positive microorganisms:

Coagulase-negative staphylococci (including Staphylococcus epidermidis)

Enterococcus faecalis

Staphylococcus aureus

Streptococcus agalactiae

Group 0 streptococci

Viridans group streptococci

Aerobic and facultative Gram-negative microorganisms:

Citrobacter amalonaticus

Citrobacter diversus

Citrobacter freundii

Klebsiella oxytoca

Klebsiella ozaenae

Nitrofurantoin is not active against most strains of Proteus species or Serratia species. It has no activity against Pseudomonas species.

Susceptibility Test Methods:

When available, the clinical microbiology laboratory should provide cumulative results of the in vitro susceptibility test results for antimicrobial drugs used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.

Dilution techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method (broth or agar) (1) or equivalent with standardized inoculum concentrations and standardized concentrations of nitrofurantoin powder. The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion technique: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure (2) requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 300 µg of nitrofurantoin to test the susceptibility of microorganisms to nitrofurantoin. The disk diffusion interpretive criteria are provided in Table 1.

Table 1.  Susceptibility Interpretive Criteria for Nitrofurantoin
Susceptibility Interpretive Criteria
Pathogen Minimum Inhibitory Concentrations (µg/mL) Disk Diffusion (zone diameter in mm)

S

I

R

S

I

R

Enterobacteriaceae

≤32

64

≥128

≥17

15-16

≤14

Staphylococcus spp.

≤32

64

≥128

≥17

15-16

≤14

A report of Susceptible indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the urine reaches the concentrations usually achievable. A report of Intermediate indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone, which prevents small, uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the urine reaches the concentrations usually achievable; other therapy should be selected.

Quality Control: Standardized susceptibility test procedures require the use of quality control microorganisms to control the technical aspects of the test procedures (3). Standard nitrofurantoin powder should provide the following range of values noted in Table 2.

Table 2.  Acceptable Quality Control Ranges for Nitrofurantoin
QC Strain Acceptable Quality Control Ranges
Minimum InhibitoryConcentration (µg/mL) Disk Diffusion(zone diameter in mm)

Escherichia coli
ATCC 25922

4 – 16

20 -25

Enterococcus faecalis
ATCC 29212

4 – 16

NAa

Staphylococcus aureus
ATCC 29213

8 – 32

NAa

Staphylococcus aureus
ATCC 25923

NAa

18-22

Dosage and administration

Nitrofurantoin monohydrate/macrocrystals capsules should be taken with food.

Adults and Pediatric Patients Over 12 Years: One 100 mg capsule every 12 hours for seven days.

Package/Label Display Panel

NITROFURANTOIN MONOHYDRATE/MACROCRYSTALLINE 
nitrofurantoin monohydrate/macrocrystalline capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68001-001
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NITROFURANTOIN (NITROFURANTOIN) NITROFURANTOIN 25 mg
NITROFURANTOIN MONOHYDRATE (NITROFURANTOIN) NITROFURANTOIN 75 mg
Inactive Ingredients
Ingredient Name Strength
CARBOMER HOMOPOLYMER TYPE B (ALLYL SUCROSE CROSSLINKED)  
STARCH, CORN  
D&C YELLOW NO. 10  
FD&C BLUE NO. 1  
FD&C RED NO. 40  
GELATIN  
LACTOSE, UNSPECIFIED FORM  
MAGNESIUM STEARATE  
POVIDONES  
TALC  
TITANIUM DIOXIDE  
Product Characteristics
Color YELLOW, BLACK Score no score
Shape CAPSULE Size 20mm
Flavor Imprint Code Macrobid;52427285
Contains     
Packaging
# Item Code Package Description
1 NDC:68001-001-00 100 CAPSULE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020064 03/20/2013
Labeler - BluePoint Laboratories (985523874)
Registrant - Alvogen, Inc. (008057330)
Establishment
Name Address ID/FEI Operations
Norwich Pharmaceuticals Inc. 132218731 ANALYSIS(68001-001), MANUFACTURE(68001-001)
Revised: 03/2017   BluePoint Laboratories
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