Indications and Usage
Nitrofurantoin Capsules USP (Macrocrystals) are specifically indicated for the treatment of urinary tract infections when due to susceptible strains of Escherichia coli, enterococci, Staphylococcus aureus, and certain susceptible strains of Klebsiella and Enterobacter species.
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 (Macrocrystals) and other antibacterial drugs, Nitrofurantoin Capsules USP (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 (Macrocrystals) are predisposed to persistence or reappearance of bacteriuria. 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 (Macrocrystals), other therapeutic agents with broader tissue distribution should be selected. In considering the use of Nitrofurantoin Capsules USP (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 (macrocrystals) should be given with food to improve drug absorption and, in some patients, tolerance.
Adults
50 to 100 mg four times a day - the lower dosage level is recommended for uncomplicated urinary tract infections.
Pediatric Patients
5 to 7 mg/kg of body weight per 24 hours, given in four divided doses (contraindicated under one month of age).
Therapy should be continued for one week or for at least 3 days after sterility of the urine is obtained. Continued infection indicates the need for reevaluation.
For long-term suppressive therapy in adults, a reduction of dosage to 50 to 100 mg at bedtime may be adequate. For long-term suppressive therapy in pediatric patients, doses as low as 1 mg/kg per 24 hours, given in a single dose or in two divided doses, may be adequate. SEE WARNINGS SECTION REGARDING RISKS ASSOCIATED WITH LONG-TERM THERAPY.
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 (macrocrystals) are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
Nitrofurantoin capsules (macrocrystals) are also contraindicated in those patients with known hypersensitivity to nitrofurantoin.
Adverse Reactions
Respiratory
CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR.
CHRONIC PULMONARY REACTIONS OCCUR GENERALLY 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 ).
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, nystagmus, dizziness, headache, and drowsiness 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.
Dermatologic
Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely. Transient alopecia also has been reported.
Allergic
A lupus-like syndrome associated with pulmonary reactions to nitrofurantoin has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; pruritus; urticaria; 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.
Gastrointestinal
Nausea, emesis, and anorexia occur most often. Abdominal pain and diarrhea are less common gastrointestinal reactions. These dose-related reactions can be minimized by reduction of dosage. Sialadenitis and pancreatitis have been reported. 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 ).
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.
Laboratory Adverse Events
The following laboratory adverse events have been reported with the use of nitrofurantoin: increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus, eosinophilia, 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 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.
Overdosage
Occasional incidents of acute overdosage of nitrofurantoin macrocrystals 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. It is dialyzable.
Description
Nitrofurantoin Capsules, USP (Macrocrystals) are a synthetic chemical of controlled crystal size. It is a stable, yellow, crystalline compound. Nitrofurantoin Capsules, USP (Macrocrystals) are an antibacterial agent for specific urinary tract infections.
Nitrofurantoin, USP (macrocrystals) is chemically designated as 2,4-Imidazolidinedione, 1-[[(5-nitro-2-furanyl)methylene]amino]- and has the following structural formula:
C8H6N4O5 (anhydrous) M.W. 238.16
Each capsule, for oral administration, contains 50 mg or 100 mg of nitrofurantoin, USP (macrocrystals). In addition, each capsule contains the following inactive ingredients: corn starch, edible black ink (black iron oxide, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, propylene glycol, shellac glaze), gelatin, lactose monohydrate, talc, titanium dioxide and colorant D&C Red No. 33.
structural formula - nitrofurantoin, USPClinical Pharmacology
Nitrofurantoin macrocrystals are a larger crystal form of nitrofurantoin. The absorption of nitrofurantoin macrocrystals is slower and its excretion somewhat less when compared to nitrofurantoin. Blood concentrations at therapeutic dosage are usually low. It is highly soluble in urine, to which it may impart a brown color.
Following a dose regimen of 100 mg q.i.d. for 7 days, average urinary drug recoveries (0 to 24 hours) on day 1 and day 7 were 37.9% and 35%.
Unlike many drugs, the presence of food or agents delaying gastric emptying can increase the bioavailability of nitrofurantoin macrocrystals, presumably by allowing better dissolution in gastric juices.
How Supplied / Storage and Handling
Nitrofurantoin Capsules USP (Macrocrystals) are available as pink opaque/white opaque capsules, imprinted with z, “Zenith 50 mg” on the cap and “2130”, underlined with a double bar, on the body, in black ink, containing 50 mg nitrofurantoin macrocrystals, packaged in bottles of 100 (NDC 0115-1643-01) and 1000 capsules (NDC 0115-1643-03).
Nitrofurantoin Capsules USP (Macrocrystals) are available as pink opaque capsules, imprinted with z, “Zenith 100 mg” on the cap and “2131”, underlined with a triple bar, on the body, in black ink, containing 100 mg nitrofurantoin macrocrystals, packaged in bottles of 100 (NDC 0115-1645-01) and 1000 capsules (NDC 0115-1645-03).
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
Patient Counseling Information
Patients should be advised to take nitrofurantoin macrocrystals with food 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.
Many patients who cannot tolerate microcrystalline nitrofurantoin are able to take nitrofurantoin macrocrystals without nausea.
Patients should be advised not to use antacid preparations containing magnesium trisilicate while taking nitrofurantoin macrocrystals.
Patients should be counseled that antibacterial drugs including nitrofurantoin macrocrystals should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When nitrofurantoin macrocrystals 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 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.