NDC 60760-194 Nitrofurantoin (monohydrate/macrocrystals)

Nitrofurantoin (monohydrate/macrocrystals)

NDC Product Code 60760-194

NDC Code: 60760-194

Proprietary Name: Nitrofurantoin (monohydrate/macrocrystals) What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Nitrofurantoin (monohydrate/macrocrystals) What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
BLACK (C48323 - IVORY)
WHITE (C48325 - IVORY)
Shape: CAPSULE (C48336)
Size(s):
21 MM
Imprint(s):
E122
Score: 1

NDC Code Structure

  • 60760 - St. Mary's Medical Park Pharmacy
    • 60760-194 - Nitrofurantoin (monohydrate/macrocrystals)

NDC 60760-194-14

Package Description: 14 CAPSULE in 1 BOTTLE, PLASTIC

NDC Product Information

Nitrofurantoin (monohydrate/macrocrystals) with NDC 60760-194 is a a human prescription drug product labeled by St. Mary's Medical Park Pharmacy. The generic name of Nitrofurantoin (monohydrate/macrocrystals) is nitrofurantoin (monohydrate/macrocrystals). The product's dosage form is capsule and is administered via oral form.

Labeler Name: St. Mary's Medical Park Pharmacy

Dosage Form: Capsule - A solid oral dosage form consisting of a shell and a filling. The shell is composed of a single sealed enclosure, or two halves that fit together and which are sometimes sealed with a band. Capsule shells may be made from gelatin, starch, or cellulose, or other suitable materials, may be soft or hard, and are filled with solid or liquid ingredients that can be poured or squeezed.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Nitrofurantoin (monohydrate/macrocrystals) Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • NITROFURANTOIN MONOHYDRATE 75 mg/1
  • NITROFURANTOIN 25 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • CARBOMER HOMOPOLYMER TYPE B (ALLYL SUCROSE CROSSLINKED) (UNII: Z135WT9208)
  • D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • FD&C RED NO. 40 (UNII: WZB9127XOA)
  • GELATIN, UNSPECIFIED (UNII: 2G86QN327L)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • TALC (UNII: 7SEV7J4R1U)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • SUCROSE (UNII: C151H8M554)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Nitrofurans - [CS]
  • Nitrofuran Antibacterial - [EPC] (Established Pharmacologic Class)
  • Nitrofurans - [CS]
  • Nitrofuran Antibacterial - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: St. Mary's Medical Park Pharmacy
Labeler Code: 60760
FDA Application Number: ANDA077066 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 04-19-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Nitrofurantoin (monohydrate/macrocrystals) Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

(Twice-A-Day Dosage)

Rx Only

Other

To reduce the development of drug-resistant bacteria and maintain the effectiveness of nitrofurantoin capsules, USP (monohydrate/macrocrystals) and other antibacterial drugs, nitrofurantoin capsules, USP (monohydrate/macrocrystals) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Description

Nitrofurantoin is an antibacterial agent specific for urinary tract infections. Nitrofurantoin capsules, USP (monohydrate/macrocrystals) are hard gelatin capsule shells containing the equivalent of 100 mg of nitrofurantoin in the form of 25 mg of nitrofurantoin macrocrystals USP and 75 mg of nitrofurantoin monohydrate USP.The chemical name of nitrofurantoin macrocrystals USP is 1-[[[5-nitro-2-furanyl]methylene]amino]-2,4-imidazolidinedione. The chemical structure is the following:Molecular Weight: 238.16The chemical name of nitrofurantoin monohydrate USP is 1-[[[5-nitro-2-furanyl]methylene]amino]-2,4-imidazolidinedione monohydrate. The chemical structure is the following:Molecular Weight: 256.17Inactive IngredientsEach capsule contains carbomer 934P, colloidal silicon dioxide, corn starch, compressible sugar, D&C yellow No. 10, edible white ink, FD&C blue No. 1, FD&C red No. 40, gelatin, lactose monohydrate, magnesium stearate, povidone, talc, and titanium dioxide.Meets USP Dissolution Test 5

Clinical Pharmacology

Each nitrofurantoin capsule (monohydrate/macrocrystals) 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 capsules (monohydrate/macrocrystals) are similar to those of the 50 mg or 100 mg nitrofurantoin (macrocrystals) capsules. 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 capsules (monohydrate/macrocrystals) 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) is 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 MicroorganismsStaphylococcus saprophyticusAerobic and Facultative Gram-Negative MicroorganismsEscherichia coliAt 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 MicroorganismsCoagulase-negative staphylococci (including


Staphylococcus epidermidis)


Enterococcus faecalisStaphylococcus aureusStreptococcus agalactiaeGroup D streptococciViridans group streptococciAerobic and Facultative Gram-Negative MicroorganismsCitrobacter amalonaticusCitrobacter diversusCitrobacter freundiiKlebsiella oxytocaKlebsiella ozaenaeNitrofurantoin 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 mcg 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 NitrofurantoinPathogenSusceptibility Interpretive CriteriaMinimum Inhibitory Concentrations (mcg/mL)Disk Diffusion (Zone diameter in mm)SIRSIREnterobacteriaceae≤3264≥128≥1715 to 16≤14Staphylococcus spp.


≤3264≥128≥1715 to 16≤14A 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 NitrofurantoinQC StrainAcceptable Quality Control RangesMinimum Inhibitory Concentration (mcg/mL)Disk Diffusion (zone diameter in mm)Escherichia coli ATCC 25922


4 to 1620 to 25Enterococcus faecalis ATCC 29212


4 to 16NA


Not applicableStaphylococcus aureus ATCC 29213


8 to 32NA


Staphylococcus aureus ATCC 25923


NA


a18 to 22

Indications And Usage

Nitrofurantoin (monohydrate/macrocrystals) is indicated only for the treatment of acute uncomplicated urinary tract infections (acute cystitis) caused by susceptible strains of


Escherichia coli or


Staphylococcus saprophyticus.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 nitrofurantoin (monohydrate/macrocrystals) and other antibacterial drugs, nitrofurantoin (monohydrate/macrocrystals) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.Nitrofurantoins lack the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with nitrofurantoin (monohydrate/macrocrystals) are predisposed to persistence or reappearance of bacteriuria (see


CLINICAL STUDIES). Urine specimens for culture and susceptibility testing should be obtained before and after completion of therapy. If persistence or reappearance of bacteriuria occurs after treatment with nitrofurantoin (monohydrate/macrocrystals), other therapeutic agents with broader tissue distribution should be selected. In considering the use of nitrofurantoin (monohydrate/macrocrystals), lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antimicrobial resistance when agents with broader tissue distribution are utilized.

Contraindications

Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug.Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38 to 42 weeks gestation), during labor and delivery, or when the onset of labor is imminent. For the same reason, the drug is contraindicated in neonates under one month of age.Nitrofurantoin (monohydrate/macrocrystals) is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.Nitrofurantoin (monohydrate/macrocrystals) is also contraindicated in those patients with known hypersensitivity to nitrofurantoin.

Warnings

Pulmonary ReactionsACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH NITROFURANTOIN. IF THESE REACTIONS OCCUR, NITROFURANTOIN (MONOHYDRATE/MACROCRYSTALS) SHOULD BE DISCONTINUED AND APPROPRIATE MEASURES TAKEN. REPORTS HAVE CITED PULMONARY REACTIONS AS A CONTRIBUTING CAUSE OF DEATH.CHRONIC PULMONARY REACTIONS (DIFFUSE INTERSTITIAL PNEUMONITIS OR PULMONARY FIBROSIS, OR BOTH) CAN DEVELOP INSIDIOUSLY. THESE REACTIONS OCCUR RARELY AND GENERALLY IN PATIENTS RECEIVING THERAPY FOR SIX MONTHS OR LONGER. CLOSE MONITORING OF THE PULMONARY CONDITION OF PATIENTS RECEIVING LONG-TERM THERAPY IS WARRANTED AND REQUIRES THAT THE BENEFITS OF THERAPY BE WEIGHED AGAINST POTENTIAL RISKS (SEE RESPIRATORY REACTIONS).

Hepatotoxicity

Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. Fatalities have been reported. The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.

Neuropathy

Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating disease may enhance the occurrence of peripheral neuropathy. Patients receiving long-term therapy should be monitored periodically for changes in renal function.Optic neuritis has been reported rarely in postmarketing experience with nitrofurantoin formulations.

Hemolytic Anemia

Cases of hemolytic anemia of the primaquine-sensitivity type have been induced by nitrofurantoin. Hemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. This deficiency is found in 10 percent of Blacks and a small percentage of ethnic groups of Mediterranean and Near-Eastern origin. Hemolysis is an indication for discontinuing nitrofurantoin (monohydrate/macrocrystals); hemolysis ceases when the drug is withdrawn.

Clostridium Difficile-Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including nitrofurantoin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of


C. difficile.


C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of


C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against


C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of


C. difficile, and surgical evaluation should be instituted as clinically indicated.

Information For Patients

Patients should be advised to take nitrofurantoin (monohydrate/macrocrystals) with food (ideally breakfast and dinner) to further enhance tolerance and improve drug absorption. Patients should be instructed to complete the full course of therapy; however, they should be advised to contact their physician if any unusual symptoms occur during therapy.Patients should be advised not to use antacid preparations containing magnesium trisilicate while taking nitrofurantoin (monohydrate/macrocrystals)


.Patients should be counseled that antibacterial drugs including nitrofurantoin (monohydrate/macrocrystals) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When nitrofurantoin (monohydrate/macrocrystals) is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by nitrofurantoin (monohydrate/macrocrystals) or other antibacterial drugs in the future.Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

General

Prescribing nitrofurantoin (monohydrate/macrocrystals) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Drug Interactions

Antacids containing magnesium trisilicate, when administered concomitantly with nitrofurantoin, reduce both the rate and extent of absorption. The mechanism for this interaction probably is adsorption of nitrofurantoin onto the surface of magnesium trisilicate.Uricosuric drugs, such as probenecid and sulfinpyrazone, can inhibit renal tubular secretion of nitrofurantoin. The resulting increase in nitrofurantoin serum levels may increase toxicity, and the decreased urinary levels could lessen its efficacy as a urinary tract antibacterial.

Drug & Or Laboratory Test Interactions

As a result of the presence of nitrofurantoin, a false-positive reaction for glucose in the urine may occur. This has been observed with Benedict’s and Fehling’s solutions but not with the glucose enzymatic test.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Nitrofurantoin was not carcinogenic when fed to female Holtzman rats for 44.5 weeks or to female Sprague-Dawley rats for 75 weeks. Two chronic rodent bioassays utilizing male and female Sprague-Dawley rats and two chronic bioassays in Swiss mice and in BDF


1 mice revealed no evidence of carcinogenicity.


Nitrofurantoin presented evidence of carcinogenic activity in female B6C3F


1 mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulosa cell tumors of the ovary. In male F344/N rats, there were increased incidences of uncommon kidney tubular cell neoplasms, osteosarcomas of the bone, and neoplasms of the subcutaneous tissue. In one study involving subcutaneous administration of 75 mg/kg nitrofurantoin to pregnant female mice, lung papillary adenomas of unknown significance were observed in the F1 generation.


Nitrofurantoin has been shown to induce point mutations in certain strains of


Salmonella typhimurium and forward mutations in L5178Y mouse lymphoma cells. Nitrofurantoin induced increased numbers of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells but not in human cells in culture. Results of the sex-linked recessive lethal assay in Drosophila were negative after administration of nitrofurantoin by feeding or by injection. Nitrofurantoin did not induce heritable mutation in the rodent models examined.


The significance of the carcinogenicity and mutagenicity findings relative to the therapeutic use of nitrofurantoin in humans is unknown.The administration of high doses of nitrofurantoin to rats causes temporary spermatogenic arrest; this is reversible on discontinuing the drug. Doses of 10 mg/kg/day or greater in healthy human males may, in certain unpredictable instances, produce a slight to moderate spermatogenic arrest with a decrease in sperm count.

Labor And Delivery

See


CONTRAINDICATIONS.

Nursing Mothers

Nitrofurantoin has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from nitrofurantoin in nursing infants under one month of age, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see


CONTRAINDICATIONS).

Pediatric Use

Nitrofurantoin (monohydrate/macrocrystals) is contraindicated in infants below the age of one month (see


CONTRAINDICATIONS). Safety and effectiveness in pediatric patients below the age of twelve years have not been established.

Geriatric Use

Clinical studies of nitrofurantoin (monohydrate/macrocrystals) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Spontaneous reports suggest a higher proportion of pulmonary reactions, including fatalities, in elderly patients; these differences appear to be related to the higher proportion of elderly patients receiving long-term nitrofurantoin therapy. As in younger patients, chronic pulmonary reactions generally are observed in patients receiving therapy for six months or longer (see


WARNINGS). Spontaneous reports also suggest an increased proportion of severe hepatic reactions, including fatalities, in elderly patients (see


WARNINGS).


In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing nitrofurantoin (monohydrate/macrocrystals). This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications (see


CONTRAINDICATIONS). Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.

Adverse Reactions

In clinical trials of nitrofurantoin (monohydrate/macrocrystals), the most frequent clinical adverse events that were reported as possibly or probably drug-related were nausea (8%), headache (6%), and flatulence (1.5%). Additional clinical adverse events reported as possibly or probably drug-related occurred in less than 1% of patients studied and are listed below within each body system in order of decreasing frequency:Gastrointestinal: Diarrhea, dyspepsia, abdominal pain, constipation, emesis


Neurologic: Dizziness, drowsiness, amblyopia


Respiratory: Acute pulmonary hypersensitivity reaction (see


WARNINGS)


Allergic: Pruritus, urticaria


Dermatologic: Alopecia


Miscellaneous: Fever, chills, malaise


The following additional clinical adverse events have been reported with the use of nitrofurantoin:Gastrointestinal: Sialadenitis, pancreatitis. There have been sporadic reports of pseudomembranous colitis with the use of nitrofurantoin. The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment (see


WARNINGS).


Neurologic: Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase the possibility of peripheral neuropathy (see


WARNINGS).


Asthenia, vertigo, and nystagmus also have been reported with the use of nitrofurantoin.Benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis, and psychotic reactions have been reported rarely. Bulging fontanels, as a sign of benign intracranial hypertension in infants, have been reported rarely.Respiratory: CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR WITH THE USE OF NITROFURANTOIN.CHRONIC PULMONARY REACTIONS GENERALLY OCCUR IN PATIENTS WHO HAVE RECEIVED CONTINUOUS TREATMENT FOR SIX MONTHS OR LONGER. MALAISE, DYSPNEA ON EXERTION, COUGH, AND ALTERED PULMONARY FUNCTION ARE COMMON MANIFESTATIONS WHICH CAN OCCUR INSIDIOUSLY. RADIOLOGIC AND HISTOLOGIC FINDINGS OF DIFFUSE INTERSTITIAL PNEUMONITIS OR FIBROSIS, OR BOTH, ARE ALSO COMMON MANIFESTATIONS OF THE CHRONIC PULMONARY REACTION. FEVER IS RARELY PROMINENT.THE SEVERITY OF CHRONIC PULMONARY REACTIONS AND THEIR DEGREE OF RESOLUTION APPEAR TO BE RELATED TO THE DURATION OF THERAPY AFTER THE FIRST CLINICAL SIGNS APPEAR. PULMONARY FUNCTION MAY BE IMPAIRED PERMANENTLY, EVEN AFTER CESSATION OF THERAPY. THE RISK IS GREATER WHEN CHRONIC PULMONARY REACTIONS ARE NOT RECOGNIZED EARLY.In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form. Upon cessation of therapy, recovery may require several months. If the symptoms are not recognized as being drug-related and nitrofurantoin therapy is not stopped, the symptoms may become more severe.Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia. Acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Resolution often is dramatic (see


WARNINGS).


Changes in EKG (e.g., non-specific ST/T wave changes, bundle branch block) have been reported in association with pulmonary reactions.Cyanosis has been reported rarely.Hepatic: Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely (see


WARNINGS).


Allergic: Lupus-like syndrome associated with pulmonary reaction to nitrofurantoin has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; anaphylaxis; arthralgia; myalgia; drug fever; chills; and vasculitis (sometimes associated with pulmonary reactions) have been reported. Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with nitrofurantoin formulations.


Dermatologic: Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely.


Hematologic: Cyanosis secondary to methemoglobinemia has been reported rarely.


Miscellaneous: As with other antimicrobial agents, superinfections caused by resistant organisms, e.g.,


Pseudomonas species or


Candida species, can occur.


In clinical trials of nitrofurantoin (monohydrate/macrocrystals), the most frequent laboratory adverse events (1% to 5%), without regard to drug relationship, were as follows: eosinophilia, increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus. The following laboratory adverse events also have been reported with the use of nitrofurantoin: 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.

Overdosage

Occasional incidents of acute overdosage of nitrofurantoin have not resulted in any specific symptoms other than vomiting. Induction of emesis is recommended. There is no specific antidote, but a high fluid intake should be maintained to promote urinary excretion of the drug. Nitrofurantoin is dialyzable.

Dosage And Administration

Nitrofurantoin capsules (monohydrate/macrocrystals) should be taken with food.Adults and Pediatric Patients Over 12 YearsOne 100 mg capsule every 12 hours for seven days.

How Supplied

Nitrofurantoin capsules, USP (monohydrate/macrocrystals), for oral administration, are available as:100 mg: Black and ivory opaque capsules imprinted “
E 122” on the cap and body and supplied as:
NDC 60760-194-14 BOTTLES OF 14Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].Dispense contents in a tight, light-resistant container as defined in the USP with a child-resistant closure, as required.KEEP OUT OF THE REACH OF CHILDREN.

References

  • Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard-Eighth Edition. CLSI document M07-A8 [ISBN 1-56238-689-1]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2009.
  • Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard -Tenth Edition. CLSI document M02-A 10 [ISBN 1-56238-688-3]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2009.
  • Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement. CLSI document M100-S19 [ISBN 1-56238-716-2]. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2010.

Clinical Studies

Controlled clinical trials comparing nitrofurantoin (monohydrate/macrocrystals) 100 mg p.o. q12h and nitrofurantoin (macrocrystals) 50 mg p.o. q6h in the treatment of acute uncomplicated urinary tract infections demonstrated approximately 75% microbiologic eradication of susceptible pathogens in each treatment group.To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.Sandoz Inc.Princeton, NJ 08540Rev. 05/17MF0122REV05/17

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