Jan 07, 2018 SF Mono is a really nice monospaced font available to Mac users within Terminal and Xcode, but you may have noticed that SF Mono is not available outside of those two apps. If you’d like to use SF Mono font elsewhere in MacOS and in other Mac apps, follow the. Mono runs on Mac, this page describes the various features available for users who want to use Mono or Mono-based technologies on macOS. Installing Mono on macOS is very simple: Download the latest Mono release for Mac Run the.pkg file and accept the terms of the license. Jan 11, 2018 The two differences of Mono-on-Mac is that you can use use MonoMac's AppKit, etc, assemblies and the active version of Xamarin Studio to develop on Mac rather than be stuck with, say, Gtk# and MonoDevelop. Those are Very Good Things.
Mono supports macOS version 10.9 (Mavericks) and later. You can use Mono on macOS to build server, console and GUI applications. Read below for the options available for GUI application development. Mar 21, 2017 Question: Q: Uninstalling Mono Framework. I installed Mono's Framework a while ago and now I'd like to uninstall it, but I have no idea how. I've been struggling for a while but I can't seem to get it. If 'mono' is not present then you have successfullly uninstalled mono. Hope this helps with newbie mac users like myself. Signs and symptoms. This syndrome is characterized by an increased susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis, and molds.
Generic Name: nitrofurantoin monohydrate
Dosage Form: capsule
Medically reviewed by Drugs.com. Last updated on Aug 1, 2019.
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To reduce the development of drug-resistant bacteria and maintain the effectiveness of nitrofurantoin monohydrate/macrocrystals capsules and other antibacterial drugs, nitrofurantoin monohydrate/macrocrystals capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Nitrofurantoin Capsules Description
Nitrofurantoin is an antibacterial agent specific for urinary tract infections. The nitrofurantoin monohydrate/macrocrystals capsules 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:
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.
FDA approved dissolution method differs from the current USP monograph dissolution methods.
Nitrofurantoin Capsules - Clinical Pharmacology
Each nitrofurantoin monohydrate/macrocrystals 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 nitrofurantoin monohydrate/macrocrystals capsule are similar to those of the 50 mg or 100 mg 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 nitrofurantoin monohydrate/macrocrystals capsules 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 nitrofurantoin monohydrate/macrocrystals capsules are administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%.
MICROBIOLOGY
Nitrofurantoin is a nitrofuran antimicrobial agent with activity against certain Gram-positive and Gram-negative bacteria.
Mechanism of Action
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.
Interactions with Other Antibiotics
Antagonism has been demonstrated in vitro between nitrofurantoin and quinolone antimicrobials. The clinical significance of this finding is unknown.
Development of Resistance
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).
Aerobic and facultative Gram-positive microorganisms:
Staphylococcus saprophyticus
Aerobic and facultative Gram-negative microorganisms:
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.
Aerobic and facultative Gram-positive microorganisms:
Coagulase-negative staphylococci (including Staphylococcus epidermidis)
Enterococcusfaecalis
Staphylococcus aureus
Streptococcus agalactiae
Group D streptococci
Viridans group streptococci
![]() Aerobic and facultative Gram-negative microorganisms:
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.
Susceptibility Testing:
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.
Indications and Usage for Nitrofurantoin Capsules
Nitrofurantoin monohydrate/macrocrystals capsules are 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 nitrofurantoin monohydrate/macrocrystals capsules and other antibacterial drugs, nitrofurantoin monohydrate/macrocrystals capsules 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.
May 27, 2011 Mack 10 - Connected For Life (Official Video) ft. Ice Cube, WC, Butch. Mack10VEVO 10,012,179 views. 50+ videos Play all Mix - mack 10 - connected fo life YouTube; Tekashi told, but so has. Mac 10 connected for life. View credits, reviews, tracks and shop for the 2002 Vinyl release of Connected For Life on Discogs. Label: Cash Money Records - 440 060 068-1. Format: Vinyl 12 Mack 10 - Connected For Life (2002, Vinyl) Discogs. May 28, 2002 “Connected For Life” is the second single track released by Mack 10 on 2002, the song features WC, Ice Cube and Butch Cassidy. The song was written by Bryon Thomas, Dedrick Rolison. Mack 10 x2 It's plain to see, you can't change me Cause I'ma be 'Connected for Life' Outro: Mack 10 Yeah!, West Connect gang for life Butch Cassidy, Mannie Fresh you a fool for this beat, boy Uh, uh, uh. The two Los Angeles rappers co-wrote 'Foe Life,' Mack 10's 1995 breakthrough hit, and united a year later with WC to form the trio Westside Connection, a West Coast gangsta rap supergroup.
Nitrofurantoins lack the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with nitrofurantoin monohydrate/macrocrystals capsules 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 nitrofurantoin monohydrate/macrocrystals capsules, other therapeutic agents with broader tissue distribution should be selected. In considering the use of nitrofurantoin monohydrate/macrocrystals capsules, 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 monohydrate/macrocrystals capsules are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
Nitrofurantoin monohydrate/macrocrystals capsules are also contraindicated in those patients with known hypersensitivity to nitrofurantoin.
Warnings
Pulmonary reactions:
ACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH NITROFURANTOIN. IF THESE REACTIONS OCCUR, NITROFURANTOIN MONOHYDRATE/MACROCRYSTALS CAPSULES 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. (SEERESPIRATORY 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. Cad programs for mac.
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 monohydrate/macrocrystals capsules; 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.
PrecautionsInformation for Patients
Patients should be advised to take nitrofurantoin monohydrate/macrocrystals capsules 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 nitrofurantoin monohydrate/macrocrystals capsules.
Patients should be counseled that antibacterial drugs including nitrofurantoin monohydrate/macrocrystals capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When nitrofurantoin monohydrate/macrocrystals capsules 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 monohydrate/macrocrystals capsules 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 monohydrate/macrocrystals capsules 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, 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.
DRUG/LABORATORY TEST INTERACTIONS
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.
Carcinogenesis, Mutagenesis, Impairment of Fertility
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.
PregnancyTeratogenic 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.
Labor and Delivery
See CONTRAINDICATIONS.
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.)
Pediatric Use
Nitrofurantoin monohydrate/macrocrystals capsules are 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.
Geriatric Use
Clinical studies of nitrofurantoin monohydrate/macrocrystals capsules 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 nitrofurantoin monohydrate/macrocrystals capsules. 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.
Adverse Reactions
In clinical trials of nitrofurantoin monohydrate/macrocrystals capsules, 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:
Gastrointestinal: Diarrhea, dyspepsia, abdominal pain, constipation, emesis
Neurologic: Dizziness, drowsiness, amblyopia
Respiratory: Acute pulmonary hypersensitivity reaction (see WARNINGS)
Allergic: Pruritus, urticaria
Dermatologic: Alopecia
Miscellaneous: Fever, chills, malaise
The following additional clinical adverse events have been reported with the use of nitrofurantoin:
Gastrointestinal: Sialadenitis, pancreatitis. 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.)
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, and nystagmus 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.
Respiratory:
CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR WITH THE USE OF NITROFURANTOIN.
CHRONIC PULMONARY REACTIONS GENERALLY OCCUR 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.)
Allergic: Lupus-like syndrome associated with pulmonary reaction to nitrofurantoin has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; 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.
Dermatologic: Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely.
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.
In clinical trials of nitrofurantoin monohydrate/macrocrystals capsules, the most frequent laboratory adverse events (1% to 5%), without regard to drug relationship, were as follows: eosinophilia, increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus. The following laboratory adverse events also have been reported with the use of nitrofurantoin: 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 request medical information or to report SUSPECTED ADVERSE REACTIONS, contact Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
Nitrofurantoin Capsules Dosage and Administration
Nitrofurantoin monohydrate/macrocrystals capsules should be taken with food.
Adults and Pediatric Patients Over 12 Years: One 100 mg capsule every 12 hours for seven days.
How is Nitrofurantoin Capsules Supplied
Nitrofurantoin monohydrate/macrocrystals capsules are available as 100 mg opaque black and yellow capsules imprinted “(band) Macrobid (band)” on one half and “52427-285” on the other.
NDC 54348-849-06 bottle of 06
NDC 54348-849-10 bottle of 10
NDC 54348-849-14 bottle of 14
Store at controlled room temperature (59° to 86°F or 15° to 30°C).
Rx Only
Clinical Studies
Controlled clinical trials comparing nitrofurantoin monohydrate/macrocrystals capsules 100 mg p.o. q12h and nitrofurantoin macrocrystals 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.
Distributed by: Alvogen, Inc.
Pine Brook, NJ 07058 USA
Rev: 08/2018 PI303-08
Package Labeling: (54348-849-06)Package Labeling: (54348-849-10)Package Labeling: (54348-849-14)
PharmPak, Inc.
Related questionsMore about nitrofurantoin
Consumer resourcesProfessional resources
Other brands:Macrobid, Macrodantin, Furadantin
Related treatment guides
Published online 2013 May 31. doi: 10.1093/cid/cit368
PMID: 23728141
This article has been cited by other articles in PMC.
Abstract
We report a case of MonoMAC syndrome in a patient with a GATA2 mutation and discuss the manifestations, diagnosis, and treatment of this novel immunodeficiency disorder.
Keywords: GATA2, MonoMAC, monocytopenia, mycobacterial infection, immunodeficiency
Monocytopenia and mycobacterial infection (MonoMAC) syndrome is caused by heterozygous mutations in GATA2, resulting in the loss of function of a gene that regulates many aspects of development from hematopoiesis to lymphatic formation. It is also known as combined dendritic cell (DC), monocyte, B and natural killer (NK) lymphoid cell deficiency; familial myelodysplasia/leukemia with lymphedema (Emberger syndrome); and familial leukemia/myelodysplasia. All of these names recognize the same recently described immunodeficiency disorder characterized by profoundly decreased or absent circulating monocytes, DCs, NK cells, and B cells, associated with an increased risk of opportunistic infections and hematological malignancies [, ]. Patients typically present during early adulthood with severe or recurrent nontuberculous mycobacterial (NTM) infections, although opportunistic fungal infections and disseminated human papillomavirus (HPV) infections also occur [, ]. Both autosomal dominant inheritance and sporadic cases have been identified [, ]. Bone marrow transplant has been curative in some cases [, ]. Here we describe a 23-year-old Asian man who presented with fever of unknown origin and was ultimately diagnosed with recurrent NTM infection due to MonoMAC syndrome. Infectious disease physicians are among the clinical specialists who are likely to encounter patients with this serious but potentially curable condition, and should become familiar with its presentation, diagnosis, and treatment.
CASE REPORT
A 23-year-old Filipino man presented to the Westchester Medical Center in June 2012 with nodular skin lesions on the anterior aspect of his distal lower extremities of approximately 4 weeks duration. He also complained of intermittent fevers (38.3°C–38.9°C), fatigue, poor appetite, and a 12-pound weight loss over the same period of time. These symptoms were preceded by several months of intermittently productive cough.
The patient had been diagnosed with disseminated Mycobacterium szulgai lung infection involving cervical and mediastinal lymph nodes in August of 2007, the same year he immigrated to the United States. Blood cell count at that time revealed lymphocytopenia (lymphocyte count: 270 cells/mm3) and monocytopenia (monocyte count: 27 cells/mm3). Two months later he developed neutropenia (nadir absolute neutrophil count: 64 cells/mm3) that responded well to treatment with granulocyte colony-stimulating factor. Bone marrow biopsy showed hypocellularity with granulocytic hypoplasia. He was successfully treated with right upper lobectomy and resection of necrotic thoracic lymph nodes in addition to 18 months of antimycobacterial therapy. Past medical history was also significant for recurrent ear infections during childhood, 4 episodes of community-acquired pneumonia since age 12, and recurrent warts on his feet and hands. His brother had had recurrent warts but was otherwise healthy. His sister and mother were healthy, but his father had died of acute bowel infarction.
On physical examination, there were bilateral knee effusions and scattered tender, erythematous, subcutaneous nodules on the pretibial areas. White blood cell count was 3000 cells/mm3 (42% neutrophils, 10% lymphocytes, 1% monocytes, 44% eosinophils, 2% bands); hemoglobin level was 12.7 g/dL; platelet count was 117 × 109/L. The CD4+ T-cell count was 141 cells/mm3 and the CD4/CD8 ratio was 0.99. Ninety-eight percent of the patient's total lymphocyte count corresponded to T cells (normal percentages: T cells 60%–80%, B cells 10%–20%, and NK cells 5%–10%), indicating B and NK lymphopenia. Electrolytes, creatinine, and liver function tests were within normal limits. HIV, hepatitis B, and hepatitis C antibody testing was negative. Serum cryptococcal antigen, serum galactomannan, urine Histoplasma antigen, and Coccidioides immitis and Histoplasma capsulatum serologies were all negative. The patient had a positive tuberculin skin test (20 mm) but the QuantiFERON-TB Gold In-Tube test was negative. Stool ova and parasite examination and Strongyloides antibody test were negative. Serum immunoglobulin M and immunoglobulin G antibodies against Coxiella burnetii and Brucella species were negative. Serum immunoglobulin levels were within the normal range. Bacterial blood cultures were negative. Synovial fluid obtained from the right knee showed 1600 white cells/mm3 with a neutrophil predominance. Bacterial, fungal, and acid-fast bacilli (AFB) cultures of the synovial fluid were negative. Antineutrophil cytoplasmic antibodies, antinuclear antibodies, complement levels and the angiotensin-converting enzyme level were within normal limits. Computed tomography of the chest showed patchy and nodular pulmonary infiltrates within the right middle, left upper, and left lower lobes with associated mediastinal lymphadenopathy measuring up to 1.2 cm in diameter. Computed tomography of the abdomen showed multiple enhancing hypervascular lesions throughout the liver measuring up to 1.2 cm and a 2.3-cm heterogeneous mass with nodular enhancement in the right lobe of the liver.
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A biopsy of the skin lesions showed panniculitis consistent with erythema nodosum; bacterial, fungal, and AFB cultures were negative. A percutaneous fine-needle aspiration biopsy of the lesions in the right hepatic lobe showed an Epstein-Barr virus (EBV)–associated smooth muscle tumor; bacterial, fungal, and AFB cultures were negative. A transbronchial biopsy of the lung showed nonnecrotizing granulomas, but fungal and AFB stains were negative. Culture from 2 of 3 separate expectorated sputum samples and from bronchoalveolar lavage (BAL) fluid yielded M. avium complex (MAC). The patient's fever, skin lesions, and respiratory and constitutional symptoms resolved within 2 weeks of anti-MAC therapy consisting of ethambutol, rifabutin, and clarithromycin. The constellation of peripheral cytopenias, recurrent NTM, HPV infections, EBV-associated smooth muscle tumors, and autoimmune phenomena led to the suspicion of MonoMAC syndrome. Genetic testing found a heterozygous mutation in GATA2 (c.1186C > T; p.R396W) confirming the diagnosis of GATA2 deficiency. This mutation has been reported previously in patients with MonoMAC syndrome []. His brother and sister tested negative for GATA2 mutations. The patient has now been referred for bone marrow transplant.
DISCUSSION
In addition to MonoMAC, other adult-onset primary immunodeficiency disorders can be associated with NTM infections. These include the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, which results from dominant gain of function mutations in chemokine receptor CXCR4 leading to retention of mature neutrophils in the bone marrow []; and a more recently described immunodeficiency syndrome characterized by the presence of anti–interferon-γ autoantibodies in Asian adults with disseminated NTM []. WHIM is unlikely to explain this patient's presentation, as he had normal serum immunoglobulin levels and a hypocellular bone marrow. Although we did not measure serum anti–interferon-γ antibodies in our patient, the presence of peripheral cytopenias, hypocellular bone marrow, and a GATA2 mutation support the diagnosis of MonoMAC.
At least 25 cases of MonoMAC have been reported [, , , ]. The main characteristics of MonoMAC syndrome are listed in Table Table1.1. At present, there does not appear to be any racial/ethnic predilection with reported cases in Whites, Asians, and Hispanics. The syndrome was first described by Vinh et al after identifying a group of 18 patients (mean age: 31 years) with disseminated NTM and other opportunistic infections []. Seventy-eight percent of the patients in this cohort developed NTM disease, with slow-growing mycobacteria accounting for most of these infections. MAC was identified in blood and/or other sterile sites in more than one-half of these cases []. Other infections seen in MonoMAC syndrome are presented in Table Table11.
Table 1.
a In the largest case series of MonoMAC syndrome (n = 18), reduced numbers of circulating monocytes (mean, 13 cells/mm3; normal, 210–660 cells/mm3), B cells (mean, 9 cells/mm3; normal, 49–424 cells/mm3) and natural killer cells (mean, 16 cells/mm3; normal, 87–505 cells/mm3) were reported [].
b Both tissue and circulating dendritic cells, with the exception of epidermal Langerhans cells [].
c A positive family history for Mycobacterium avium complex or myelodysplastic syndrome/acute myeloid leukemia, the presence of profound monocytopenia, cytogenetic abnormalities in a hypoplastic bone marrow, and GATA2 mutations favor the diagnosis of MonoMAC over idiopathic CD4+ lymphocytopenia [].
Noninfectious conditions have also been described in MonoMAC [, , , ] (Table (Table1).1). Erythema nodosum and pulmonary alveolar proteinosis have each been seen in up to one-third of patients [] and can be the presenting feature []. Patients with pulmonary alveolar proteinosis, including those without documented GATA2 mutations, have an increased risk of opportunistic fungal and mycobacterial infections [].
Profound peripheral blood monocytopenia and B and NK cell lymphopenia are characteristic of patients with MonoMAC [, , , ]. Notably, monocytopenia in these patients can exist for more than a decade before a diagnosis is made []. Other cytopenias seen in MonoMAC are listed in Table Table1.1. Despite the near absence of circulating monocytes and DCs, tissue macrophages and epidermal Langerhans cells are preserved in MonoMAC [, , ]. Similarly, despite marked B-cell lymphopenia, serum immunoglobulin levels remain within normal limits and tissue plasma cells remain detectable in skin and bone marrow biopsies of patients with MonoMAC [, ]. Although it is unknown whether tissue NK cells are also spared in MonoMAC, our patient had detectable NK cells in synovial fluid.
The bone marrow of patients with MonoMAC is characterized by hypocellularity, fibrosis, and multilineage dysplasia [, , ]. Cytogenetic abnormalities are common [, ]. Progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is one of the most serious complications of this syndrome. One-half of the 18 patients reported by Vinh et al were diagnosed with MDS/AML by age 32, and complications associated with hematological malignancy accounted for 4 of the 5 deaths in this cohort []. Conceivably, some of the previous reports of NTM infections in patients with MDS/AML [] might represent unrecognized cases of GATA2 mutation.
Mortality of MonoMAC syndrome can be as high as 28% []. Allogeneic hematopoietic stem cell transplantation has been shown to be an effective strategy to reconstitute the depleted hematopoietic compartments and reverse the clinical phenotype seen in affected patients [, ]. It is unknown whether there is any role for the use of growth factors such as granulocyte macrophage colony-stimulating factor to correct the peripheral monocytopenia, whether antimicrobial prophylaxis against MAC and specific immunization protocols (eg, HPV vaccination) are indicated, or whether prevention of infections can prevent neoplastic complications later in life.
Notes
Acknowledgments. Because of space constraints, we regret our inability to cite other excellent papers that have also examined the clinical significance of GATA2 mutations.
Financial support. This work was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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