DailyMed Label: Macrobid

DailyMed Label: Macrobid

2023

DailyMed Prescription

Macrobid

Nitrofurantoin Monohydrate/Macrocrystalline

Almatica Pharma LLC

NDC: 52427-285

NDC: 52427-285

NDC: 52427-285

NDC: 52427-285

NDC: 52427-285

Nitrofurantoin is an antibacterial agent specific for urinary tract infections. Macrobid ® (Nitrofurantoin Capsules, USP) (monohydrate/macrocrystals) is a hard gelatin capsule.  Each capsule contains 100 mg of nitrofurantoin 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: Molecular Weight: 238.16 The chemical name of nitrofurantoin monohydrate is 1-[[[5-nitro-2-furanyl]methylene]amino]-2,4- imidazolidinedione monohydrate. The chemical structure is the following: Molecular Weight: 256.17 Inactive Ingredients: Each capsule contains carbomer 934P, corn starch, compressible sugar, D&C Yellow No. 10, edible gray ink, FD&C Blue No. 1, FD&C Red No. 40, gelatin, lactose, magnesium stearate, povidone, talc, and titanium dioxide. Meets USP Dissolution Test 8.

Macrobid is 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 Macrobid and other antibacterial drugs, Macrobid 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 Macrobid 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 Macrobid , other therapeutic agents with broader tissue distribution should be selected. In considering the use of Macrobid , 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.

Macrobid capsules should be taken with food. Adults and Pediatric Patients Over 12 Years : One 100 mg capsule every 12 hours for seven days.

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. Macrobid is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin. Macrobid is also contraindicated in those patients with known hypersensitivity to nitrofurantoin.

Patients should be advised to take Macrobid 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 Macrobid . Patients should be counseled that antibacterial drugs including Macrobid should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Macrobid 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 Macrobid 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. Prescribing Macrobid 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. 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. 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. 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 BDF 1 mice revealed no evidence of carcinogenicity. Nitrofurantoin presented evidence of carcinogenic activity in female B6C3F 1 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. Teratogenic effects: 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. See CONTRAINDICATIONS . 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. ) Macrobid is 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. Clinical studies of Macrobid 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 Macrobid . 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.

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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.

Macrobid (Nitrofurantoin Capsules, USP) (monohydrate/macrocrystals) is available as 100 mg opaque black and yellow capsules imprinted “(band) Macrobid (band)” on one half and “52427-285” on the other. NDC 52427-285-01  bottle of 100 Store at controlled room temperature 15°C to 30°C (59°F to 86°F). Rx only

Each Macrobid capsule 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 Macrobid capsule are similar to those of 50 mg or 100 mg Macrodantin ® (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 Macrobid capsule 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 Macrobid is administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%. Nitrofurantoin is a nitrofuran antimicrobial agent with activity against certain Gram-positive and Gram-negative bacteria. The mechanism of the antimicrobial action of nitrofurantoin is unusual among antibacterials. Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other macromolecules. As a result of such inactivations, the vital biochemical processes of protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited. Nitrofurantoin is bactericidal in urine at therapeutic doses. The broad-based nature of this mode of action may explain the lack of acquired bacterial resistance to nitrofurantoin, as the necessary multiple and simultaneous mutations of the target macromolecules would likely be lethal to the bacteria. Antagonism has been demonstrated in-vitro between nitrofurantoin and quinolone antimicrobials. The clinical significance of this finding is unknown. Development of resistance to nitrofurantoin has not been a significant problem since its introduction in 1953. Cross-resistance with antibiotics and sulfonamides has not been observed, and transferable resistance is, at most, a very rare phenomenon. Nitrofurantoin has been shown to be active against most strains of the following bacteria both in-vitro and in clinical infections (see INDICATIONS AND USAGE ): Staphylococcus saprophyticus Escherichia coli At least 90 percent of the following microorganisms exhibit an in-vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for nitrofurantoin.  However, the efficacy of nitrofurantoin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled trials. Coagulase -negative staphylococci  (including Staphylococcus epidermidis ) Enterococcus faecalis Staphylococcus aureus Streptococcus agalactiae Group D streptococci Viridans group streptococci Citrobacter amalonaticus Citrobacter diversus Citrobacter freundii Klebsiella oxytoca Klebsiella ozaenae Nitrofurantoin is not active against most strains of Proteus species or Serratia species. It has no activity against Pseudomonas species. For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Controlled clinical trials comparing Macrobid 100 mg p.o. q12h and Macrodantin 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.

NDC 52427- 285 -01 Rx only 100 mg Macrobid ® (Nitrofurantoin Capsules, USP) (monohydrate/macrocrystals) URINARY TRACT ANTIBACTERIAL 100 Capsules Almatica ®