Nitrofurantoin (Monohydrate/Macrocrystals)- Nitrofurantoin Monohydrate/Macrocrystals capsule prescribing information
INDICATIONS AND USAGE
Nitrofurantoin capsules, USP (monohydrate/macrocrystals) are 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 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 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 capsules, USP (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 capsules, USP (monohydrate/macrocrystals), other therapeutic agents with broader tissue distribution should be selected. In considering the use of nitrofurantoin capsules, USP (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.
DOSAGE AND ADMINISTRATION
Nitrofurantoin capsules (monohydrate/macrocrystals) should be taken with food.
Adults and Pediatric Patients Over 12 Years: One 100 mg capsule every 12 hours for seven days.
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 capsules (monohydrate/macrocrystals) are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
Nitrofurantoin capsules (monohydrate/macrocrystals) are also contraindicated in those patients with known hypersensitivity to nitrofurantoin.
ADVERSE REACTIONS
In clinical trials of nitrofurantoin, 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, 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.
To request medical information or to report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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/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.
DESCRIPTION
Nitrofurantoin, USP is an antibacterial agent specific for urinary tract infections. Nitrofurantoin capsules, USP (monohydrate/macrocrystals) are a hard gelatin capsule shell containing the equivalent of 100 mg of nitrofurantoin, USP 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:
The chemical name of nitrofurantoin monohydrate is 1-[[[5-nitro-2-furanyl]methylene]amino]-2,4- imidazolidinedione monohydrate. The chemical structure is the following:
Inactive Ingredients: Each capsule contains carbomer 934P, carboxymethylcellulose, corn starch, D&C Yellow No. 10, FD&C Red No. 40, gelatin, iron oxide black, iron oxide yellow, lactose, magnesium stearate, maltodextrin, povidone, sodium lauryl sulfate, sugar, talc and titanium dioxide. The black monogramming ink contains butyl alcohol, dehydrated alcohol, iron oxide black, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac and strong ammonia solution. The white monogramming ink contains butyl alcohol, dehydrated alcohol, isopropyl alcohol, povidone, propylene glycol, shellac, sodium hydroxide and titanium dioxide.
Meets USP Dissolution Test 7.
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 capsule (monohydrate/macrocrystals) are similar to those of 50 mg or 100 mg 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 (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 is administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%.
CLINICAL STUDIES
Controlled clinical trials comparing nitrofurantoin 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.
Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807
Rev. 06-2023-04
HOW SUPPLIED
Nitrofurantoin capsules, USP (monohydrate/macrocrystals), 100 mg, are supplied as a gray opaque cap and yellow opaque body imprinted axially “AN” in white ink on the cap and “478” in black ink on the body. They are available as follows:
Bottles of 100: NDC 65162-478-10
Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in tight container.
Rx Only
