Nitrofurantoin Monohydrate/Macrocrystalline (nitrofurantoin 25 mg nitrofurantoin monohydrate 75 mg) Dailymed

Precautions:

Information for Patients

Patients should be advised to take nitrofurantoin monohydrate/macrocrystals capsules 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 capsules.

Patients should be counseled that antibacterial drugs including nitrofurantoin monohydrate/macrocrystals capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When nitrofurantoin monohydrate/macrocrystals capsules are 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 capsules 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 capsules 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/ 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 BDF₁ mice revealed no evidence of carcinogenicity.

Nitrofurantoin presented evidence of carcinogenic activity in female B6C3F₁ 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.

Pregnancy:

Pregnancy Category B. Several reproduction studies have been performed in rabbits and rats at doses up to six times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to nitrofurantoin. In a single published study conducted in mice at 68 times the human dose (based on mg/kg administered to the dam), growth retardation and a low incidence of minor and common malformations were observed. However, at 25 times the human dose, fetal malformations were not observed; the relevance of these findings to humans is uncertain. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nitrofurantoin has been shown in one published transplacental carcinogenicity study to induce lung papillary adenomas in the F1 generation mice at doses 19 times the human dose on a mg/kg basis. The relationship of this finding to potential human carcinogenesis is presently unknown. Because of the uncertainty regarding the human implications of these animal data, this drug should be used during pregnancy only if clearly needed.

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 capsules are 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 capsules 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 capsules. 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 capsules, 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 uled 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 capsules, 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 Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 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.

How Supplied:

Nitrofurantoin monohydrate/macrocrystals capsules are available as 100 mg opaque black and yellow capsules imprinted “(band) Macrobid (band)” on one half and “52427-285” on the other.

NDC 68001-001-00 bottle of 100

Store at controlled room temperature (59°F to 86°F or 15°C to 30°C).

Rx Only

Clinical Studies

Controlled clinical trials comparing nitrofurantoin monohydrate/ macrocrystals capsules 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. 

Manufactured by: Norwich Pharmaceuticals, Inc.

6826 State Highway 12

Norwich, NY 13815 USA

for BluePoint Laboratories

Rev: 03/2019 PI001-02

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