Nitrofurantoin Comp

Nitrofurantoin:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Storage
• References
• Nitrofurantoin Comp (Nitrofurantoin) reviews

INDICATIONS AND USAGE

Nitrofurantoin Comp (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 Comp (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 Comp (Nitrofurantoin) macrocrystals and other antibacterial drugs, Nitrofurantoin Comp (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 Comp (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 Comp (Nitrofurantoin) macrocrystals, other therapeutic agents with broader tissue distribution should be selected. In considering the use of Nitrofurantoin Comp (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.

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 Comp (Nitrofurantoin) macrocrystals is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with Nitrofurantoin Comp (Nitrofurantoin).

Nitrofurantoin Comp (Nitrofurantoin) macrocrystals is also contraindicated in those patients with known hypersensitivity to Nitrofurantoin Comp (Nitrofurantoin).

WARNINGS

Pulmonary Reactions

ACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH Nitrofurantoin Comp. IF THESE REACTIONS OCCUR, Nitrofurantoin Comp (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.

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, 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 Comp (Nitrofurantoin) formulations.

Hemolytic Anemia

Cases of hemolytic anemia of the primaquine-sensitivity type have been induced by Nitrofurantoin Comp (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 Comp (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 Comp (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.

PRECAUTIONS

Information for Patients

Patients should be advised to take Nitrofurantoin Comp 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 Comp (Nitrofurantoin) are able to take Nitrofurantoin Comp (Nitrofurantoin) macrocrystals without nausea.

Patients should be advised not to use antacid preparations containing magnesium trisilicate while taking Nitrofurantoin Comp (Nitrofurantoin) macrocrystals.

Patients should be counseled that antibacterial drugs including Nitrofurantoin Comp (Nitrofurantoin) macrocrystals should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Nitrofurantoin Comp (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 Comp (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.

General

Prescribing Nitrofurantoin Comp (Nitrofurantoin) 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 Comp, reduce both the rate and extent of absorption. The mechanism for this interaction probably is adsorption of Nitrofurantoin Comp (Nitrofurantoin) onto the surface of magnesium trisilicate.

Uricosuric drugs, such as probenecid and sulfinpyrazone, can inhibit renal tubular secretion of Nitrofurantoin Comp (Nitrofurantoin). The resulting increase in Nitrofurantoin Comp (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 Comp (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 Comp 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 Comp (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 Comp (Nitrofurantoin) to pregnant female mice, lung papillary adenomas of unknown significance were observed in the F1 generation.

Nitrofurantoin Comp (Nitrofurantoin) has been shown to induce point mutations in certain strains of Salmonella typhimurium and forward mutations in L5178Y mouse lymphoma cells. Nitrofurantoin Comp (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 Comp (Nitrofurantoin) by feeding or by injection. Nitrofurantoin Comp (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 Comp (Nitrofurantoin) in humans is unknown.

The administration of high doses of Nitrofurantoin Comp (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

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 Comp. 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 Comp (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 Comp has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from Nitrofurantoin Comp (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 Comp (Nitrofurantoin) macrocrystals is contraindicated in infants below the age of one month (see CONTRAINDICATIONS).

Geriatric Use

Clinical studies of Nitrofurantoin Comp (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 Comp (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 Comp (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.

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 Comp 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, 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 Comp (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 Comp has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; pruritus; urticaria; anaphylaxis; arthralgia; myalgia; drug fever; and chills have been reported. Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with Nitrofurantoin Comp (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 Comp (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 Comp (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.

OVERDOSAGE

Occasional incidents of acute overdosage of Nitrofurantoin Comp (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.

DOSAGE AND ADMINISTRATION

Nitrofurantoin Comp 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.

HOW SUPPLIED

Nitrofurantoin Comp (Nitrofurantoin) Macrocrystals Capsules USP are available as pink opaque/white opaque capsules, imprinted with

, “Zenith 50 mg” on the cap and “2130”, underlined with a double bar, on the body, in black ink, containing 50 mg Nitrofurantoin Comp (Nitrofurantoin) macrocrystals, packaged in bottles of 100 and 1000 capsules and unit-dose boxes of 100 capsules.

Nitrofurantoin Comp (Nitrofurantoin) Macrocrystals Capsules USP are available as pink opaque capsules, imprinted with

, “Zenith 100 mg” on the cap and “2131”, underlined with a triple bar, on the body, in black ink, containing 100 mg Nitrofurantoin Comp (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).

STORAGE

Store at 20° to 25°C (68° to 77°F).

REFERENCES

1.) 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.

2.) 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.

3.) 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.

To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at tel: 1-888-838-2872, x6351 or drug.safetyNitrofurantoin Comp (Nitrofurantoin)tevausa.com; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Manufactured In Israel By:

TEVA PHARMACEUTICAL IND. LTD.

Jerusalem, 91010, Israel

Manufactured For:

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. E 6/2011

Nitrofurantoin Comp (Nitrofurantoin) Macro. 50mg Cap

Nitrofurantoin Comp (Nitrofurantoin) Structural Formula Imprinted logo Imprinted logo

Sulfadiazine:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Nitrofurantoin Comp (Sulfadiazine) reviews

INDICATIONS AND USAGE

Nitrofurantoin Comp (Sulfadiazine) tablets USP are indicated in the following conditions:

Chancroid

Trachoma

Inclusion conjunctivitis

Nocardiosis

Urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) in the absence of obstructive uropathy or foreign bodies, when these infections are caused by susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Staphylococcus aureus, Proteus mirabilis and P. vulgaris. Nitrofurantoin Comp (Sulfadiazine) should be used for urinary tract infections only after use of more soluble sulfonamides has been unsuccessful.

Toxoplasmosis encephalitis in patients with and without acquired immunodeficiency syndrome, as adjunctive therapy with pyrimethamine.

Malaria due to chloroquine-resistant strains of Plasmodium falciparum, when used as adjunctive therapy.

Prophylaxis of meningococcal meningitis when sulfonamide-sensitive group A strains are known to prevail in family groups or larger closed populations (the prophylactic usefulness of sulfonamides when group B or C infections are prevalent is not proved and may be harmful in closed population groups).

Meningococcal meningitis, when the organism has been demonstrated to be susceptible.

Acute otitis media due to Haemophilus influenzae, when used concomitantly with adequate doses of penicillin.

Prophylaxis against recurrences of rheumatic fever, as an alternative to penicillin.

H. influenzae meningitis, as adjunctive therapy with parental streptomycin.

IMPORTANT NOTES

In vitro sulfonamide susceptibility tests are not always reliable. The test must be carefully coordinated with bacteriologic and clinical response. When the patient is already taking sulfonamides, follow-up cultures should have aminobenzoic acid added to the culture media.

Currently, the increasing frequency of resistant organisms limits the usefulness of antibacterial agents, including the sulfonamides, especially in the treatment of recurrent and complicated urinary tract infections.

Wide variation in blood levels may result with identical doses. Blood levels should be measured in patients receiving sulfonamides for serious infections. Free sulfonamide blood levels of 5 mg to 15 mg per 100 mL may be considered therapeutically effective for most infections and blood levels of 12 mg to 15 mg per 100 mL may be considered optimal for serious infections. Twenty mg per 100 mL should be the maximum total sulfonamide level, since adverse reactions occur more frequently above this level.

CONTRAINDICATIONS

Nitrofurantoin Comp (Sulfadiazine) is contraindicated in the following circumstances: Hypersensitivity to sulfonamides.

In infants less than 2 months of age (except as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis).

In pregnancy at term and during the nursing period, because sulfonamides cross the placenta and are excreted in breast milk and may cause kernicterus.

WARNINGS

The sulfonamides should not be used for the treatment of group A betahemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever and glomerulonephritis.

Deaths associated with the administration of sulfonamides have been reported from hypersensitivity reactions, agranulocytosis, aplastic anemia and other blood dyscrasias.

The presence of such clinical signs as sore throat, fever, pallor, purpura or jaundice may be early indications of serious blood disorders.

The frequency of renal complications is considerably lower in patients receiving the more soluble sulfonamides.

PRECAUTIONS

General

Sulfonamides should be given with caution to patients with impaired renal or hepatic function and to those with severe allergy or bronchial asthma.

Hemolysis may occur in individuals deficient in glucose-6-phosphate dehydrogenase. This reaction is dose related.

Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation.

Information for Patients

Patients should be instructed to drink an eight ounce glass of water with each dose of medication and at frequent intervals throughout the day. Caution patients to report promptly the onset of sore throat, fever, pallor, purpura or jaundice when taking this drug, since these may be early indications of serious blood disorders.

Laboratory Tests

Complete blood counts and urinalyses with careful microscopic examinations should be done frequently in patients receiving sulfonamides.

Drug Interactions

Administration of a sulfonamide may increase the effect of oral anticoagulants and methotrexate, probably by displacement of these drugs from binding sites on plasma albumin. Potentiation of the action of sulfonylurea hypoglycemic agents, thiazide diuretics and uricosuric agents may also be noted. This may also be due to displacement of the drugs from albumin or a pharmacodynamic mechanism may play a role. Conversely, agents such as indomethacin, probenecid and salicylates may displace sulfonamides from plasma albumin and increase the concentrations of free drug in plasma.

Carcinogenesis, Mutagenesis, Impairment of Fertility

The sulfonamides bear certain chemical similarities to some goitrogens. Rats appear to be especially susceptible to the goitrogenic effects of sulfonamides and long-term administration has produced thyroid malignancies in rats.

Pregnancy

Teratogenic Effects

Pregnancy Category C

The safe use of sulfonamides in pregnancy has not been established. The teratogenic potential of most sulfonamides has not been thoroughly investigated in either animals or humans. However, a significant increase in the incidence of cleft palate and other bony abnormalities in offspring has been observed when certain sulfonamides of the short, intermediate and long acting types were given to pregnant rats and mice in high oral doses.

Nursing Mothers

Nitrofurantoin Comp (Sulfadiazine) is contraindicated for use in nursing mothers because the sulfonamides cross the placenta, are excreted in breast milk and may cause kernicterus.

Because of the potential for serious adverse reactions in nursing infants from Nitrofurantoin Comp (Sulfadiazine), 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 Comp (Sulfadiazine) is contraindicated in infants less than 2 months of age (except as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis). See CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION.

ADVERSE REACTIONS

Blood Dyscrasias

Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, hemolytic anemia, purpura, hypoprothrombinemia and methemoglobinemia.

Allergic Reactions

Erythema multiforme, generalized skin eruptions, epidermal necrolysis, urticaria, serum sickness, pruritus, exfoliative dermatitis, anaphylactoid reactions, periorbital edema, conjunctival and scleral injection, photosensitization, arthralgia, allergic myocarditis, drug fever and chills.

Gastrointestinal Reactions

Nausea, emesis, abdominal pains, hepatitis, diarrhea, anorexia, pancreatitis and stomatitis.

C.N.S. Reactions

Headache, peripheral neuritis, mental depression, convulsions, ataxia, hallucinations, tinnitus, vertigo and insomnia.

Renal

Crystalluria, stone formation, toxic nephrosis with oliguria and anuria; periarteritis nodosa and lupus erythematosus phenomenon have been noted.

Miscellaneous Reactions

The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Goiter production, diuresis, and hypoglycemia have occurred rarely in patients receiving sulfonamides. Cross-sensitivity may exist with these agents.

DOSAGE AND ADMINISTRATION

SYSTEMIC SULFONAMIDES ARE CONTRAINDICATED IN INFANTS UNDER 2 MONTHS OF AGE except as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis.

Usual Dosage for Infants over 2 Months of Age and Children

Initially, one-half the 24-hour dose. Maintenance, 150 mg/kg or 4 g/m2, divided into 4 to 6 doses, every 24 hours, with a maximum of 6 g every 24 hours. Rheumatic fever prophylaxis, under 30 kg, 500 mg every 24 hours; over 30 kg (66 pounds), 1 g every 24 hours.

Usual Adult Dosage

Initially, 2 g to 4 g. Maintenance, 2 g to 4 g, divided into 3 to 6 doses, every 24 hours.

HOW SUPPLIED

Nitrofurantoin Comp (Sulfadiazine) Tablets USP for oral administration are available as:

500 mg: white, unscored, capsule-shaped tablets, debossed “E 757” on one face and supplied as:

NDC 0185-0757-30 bottles of 30

NDC 0185-0757-01 bottles of 100

NDC 0185-0757-10 bottles of 1000

Storage: Store at 20° to 25°C (68° to 77°F).

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

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.

Manufactured for

Sandoz Inc.

Princeton, NJ 08540

Manufactured by

Epic Pharma, LLC

Laurelton, NY 11413

OS7190

Rev. 03/12

MF0757REV03/12

MG #16918

NDC 0185-0757-30

Nitrofurantoin Comp (Sulfadiazine) Tablets, USP

500 mg

Rx only

30 Tablets

Sandoz

500 mg x 30 Tablets