Macrobid Information
Macrobid ()
Macrobid () Description:
Nitrofurantoin is an antibacterial agent specific for urinary tract infections. The brand of nitrofurantoin is a hard gelatin capsule shell containing the equivalent of 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:
The chemical name of nitrofurantoin monohydrate is 1-[[[5-nitro-2-furanyl]methylene]amino]-2,4- imidazolidinedione monohydrate. The chemical structure is the following:
Macrobid () Clinical Pharmacology:
Each 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 capsule are similar to those of the 50 mg or 100 mg (nitrofurantoin macrocrystals) capsule. Approximately 20-25% 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 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 is administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%.
Macrobid () Indications And Usage:
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 and other antibacterial drugs, 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 are predisposed to persistence or reappearance of bacteriuria. (See .) 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 , other therapeutic agents with broader tissue distribution should be selected. In considering the use of , 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 () 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 (38-42 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 () Warnings:
ACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH NITROFURANTOIN. IF THESE REACTIONS OCCUR, Macrobid () 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 )
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.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
Macrobid () Precautions:
Patients should be advised not to use antacid preparations containing magnesium trisilicate while taking
Patients should be counseled that antibacterial drugs including should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When 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 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:
Macrobid ()
Drug Interactions:
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:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
1
Nitrofurantoin presented evidence of carcinogenic activity in female B6C3F 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 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.
Labor and Delivery:
Nursing Mothers:
Pediatric Use: Macrobid ()
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 . 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 ). Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
Macrobid () Adverse Reactions:
In clinical trials of , 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 listed below within each body system in order of decreasing frequency:
The following additional clinical adverse events have been reported with the use of nitrofurantoin:
Macrobid () 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.
Macrobid () How Supplied:
Meets USP Dissolution Test 2
Rx Only
Macrobid () Clinical Studies:
Controlled clinical trials comparing 100 mg p.o. q12h and 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.
Mfg. By: Norwich Pharmaceuticals, Inc.North Norwich, NY 13814Dist. by: TM Owner, Cincinnati, OH 45202
REVISED January 2009
