nitrofurantoin macrocrystals 100 MG Oral Capsule

Generic Name: NITROFURANTOIN MACROCRYSTALS
Brand Name: Nitrofurantoin Macrocrystals
  • Substance Name(s):
  • NITROFURANTOIN

WARNINGS

Pulmonary Reactions ACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH NITROFURANTOIN.

IF THESE REACTIONS OCCUR, NITROFURANTOIN 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If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.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Hemolysis is an indication for discontinuing nitrofurantoin macrocrystals; hemolysis ceases when the drug is withdrawn.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.

DRUG INTERACTIONS

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 macrocrystals is a synthetic chemical of controlled crystal size.

It is a stable, yellow, crystalline compound.

Nitrofurantoin macrocrystals is an antibacterial agent for specific urinary tract infections.

It is chemically designated as 1-[[(5-nitro-2-furanyl)methylene]amino]-2,4-imidazolidinedione and has the following structural formula: C8H6N4O5 M.W.

238.16 Each capsule, for oral administration, contains 50 mg or 100 mg of nitrofurantoin 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), gelatin, lactose monohydrate, silicon dioxide, sodium lauryl sulfate, talc, titanium dioxide and colorant D&C Red No.

33.

Nitrofurantoin Structural Formula

HOW SUPPLIED

Nitrofurantoin Macrocrystals Capsules USP are available as pink opaque/white opaque capsules, imprinted with , “50 mg” and “2130”, containing 50 mg nitrofurantoin macrocrystals, packaged in bottles of 100 and 1000 capsules and unit-dose boxes of 100 capsules.

Nitrofurantoin Macrocrystals Capsules USP are available as pink opaque capsules, imprinted with , “100 mg” and “2131”, containing 100 mg nitrofurantoin macrocrystals, packaged in bottles of 100 and 1000 capsules and unit-dose boxes of 100 capsules.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Imprinted logo Imprinted logo

GERIATRIC USE

Geriatric Use Clinical studies of nitrofurantoin 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 should be considered when prescribing nitrofurantoin 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 C ONTRAINDICATIONS).

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

INDICATIONS AND USAGE

Nitrofurantoin macrocrystals is 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 macrocrystals and other antibacterial drugs, nitrofurantoin 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 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 macrocrystals, other therapeutic agents with broader tissue distribution should be selected.

In considering the use of nitrofurantoin 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.

PEDIATRIC USE

Pediatric Use Nitrofurantoin macrocrystals is contraindicated in infants below the age of one month (see CONTRAINDICATIONS).

PREGNANCY

Pregnancy Teratogenic Effects 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.

Non-Teratogenic Effects 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.

NUSRING MOTHERS

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).

INFORMATION FOR PATIENTS

Information for Patients 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 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 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.

DOSAGE AND ADMINISTRATION

Nitrofurantoin 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.