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nitrofurantoin (Macrodantin, Macrobid)

Tradename: Macrodantin. Indications: - bacterial infections due to susceptible organisms - treatment of uncompliced urinary tract infection (UTI) - not as effective as ciprofloxacin [12] - prevention of frequently occurring UTI when long-term therapy is necessary Contraindications: 1) avoid in patients with creatinine clearance < 60 mL/min - not a good choice for elderly patients [9,12]* - no loss in efficacy when creatinine clearance is 40 mL/min [12] - may be safely used in elderly if eGFR > 30 mL/min provided duration of therapy < 8 days [14] 2) glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) 3) 1st trimester of pregnancy - nitrofurantoin associated with birth defects in case control studies - not duplicated in studies of asymptomatic bacteriuria [13] 4) 3rd trimester of pregnancy [11] - pregnant patients at term (38-42 weeks gestation), during labor & delivery, or when the onset of labor is imminent 5) neonates under one month of age [9] 6) pyelonephritis: insufficient levels in renal tissue [11] * MKSAP17 recommends nitrofurantoin to treat cystitis in older women [11,12] Dosage: - 50 mg PO QID - Pediatrics: 5-7 mg/kg/day divided QID Tabs: 25, 50, 100 mg Liquid: 25 mg/5 mL Sustained-release: (macro-crystalline): Tradename Macrobid - 100 mg PO BID Max 400 mg/day. Maintenance dose following dialysis. Tabs: 100 mg. Pharmacokinetics: 1) well absorbed orally 2) macrocrystal absorbed slower than micro-crystal, causing less GI distress 3) better absorbed when taken with food 4) 20-60% bound to plasma proteins 5) 50-70% metabolized by body tissue 6) 50% eliminated unchanged in the urine 7) more active in acid urine pH 8) elimination 1/2life 20 minutes to 1 hour 9) removed by hemodialysis 10) less effective in patients with creatinine clearance < 40 [5] < 60 [6] mL/min* (NOT a good drug for treatment of UTI in the elderly) * ref [12] finds nitrofurantoin inferior to ciprofloxacin for treatment of cystitis in older women independent of renal function Monitor: - liver function tests periodically [10] Antimicrobial activity: Gram positive - Streptococcus - Streptococcus group A - Streptococcus group B - Streptococcus group C - Streptococcus group G - Streptococcus pneumonia - Enterococcus faecalis (+/-) - Staphylococcus aureus (MSSA) Gram negative - Neisseria gonorrhoeae - Escherichia coli - Klebsiella species (+/-) - Enterobacter species* * Most strains of Proteus, Pseudomonas, Klebsiella & Enterobacter are resistant Adverse effects: 1) common (> 10%) a) chest pains b) chills c) cough d) fever e) difficulty breathing f) dyspepsia g) diarrhea h) loss of appetite i) nausea/vomiting j) rash 2) less common (1-10%) - sore throat, tiredness, weakness, drowsiness, headache, dizziness, numbness, paresthesias 3) uncommon (< 1%) - hemolytic anemia in patients with G6PD deficiency, hepatitis, pruritus, arthralgias, hypersensitivity & in infants < 4 weeks of age [17] 4) pulmonary [3]* - acute, subacute & chronic interstitial lung disease - acute - mean duration of exposure until symptom onset is 9 days - fever, chills, cough, dyspnea, hypoxemia, chest pain - eosinophilia (30%) - non-cardiogenic pulmonary edema, pleural effusion - reticulonodular changes on chest X-ray - oftens resolves with discontinuation, but will recur with repeat administration - chronic - onset months to years after prolonged exposure - pulmonary fibrosis (chronic) - ground glass opacities - glucocorticoids may be of benefit [11] 5) other [4] - abdominal cramps, bladder irritation, peripheral neuropathy, gout, blood dyscrasia, hepatoxicity [8] * Pulmonary function testing: 1) obstructive pattern with acute reaction 2) restrictive pattern with chronic reaction Drug interactions: 1) probenecid decreases renal excretion 2) Mg+2-containing antacids decreases absorption 3) quinolones (antagonistic) Mechanism of action: 1) may disrupt cell wall formation 2) may interfere with bacterial carbohydrate metabolism 3) bacteriostatic at low concentrations 4) bactericidal at higher concentrations

Interactions

drug interactions drug adverse effects of nitrofurantoin

General

5-nitrofuran other antibiotic

Properties

MISC-INFO: elimination route KIDNEY LIVER elimination by hemodialysis + 1/2life 0.3-1 HOURS pregnancy-category B safety in lactation +

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 761, 762
  4. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  5. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  6. AHFS Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1999
  7. Prescriber's Letter 15(9): 2008 Macrobid vs. Macrodantin Detail-Document#: 240903 (subscription needed) http://www.prescribersletter.com
  8. Chalasani N et al. for the Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008 Dec; 135:1924. PMID: 18955056
  9. FDA > Macrobid http://www.drugs.com/pro/macrobid.html
  10. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  11. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18. American College of Physicians, Philadelphia 2012, 2015, 2018.
  12. Singh N et al. Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women. CMAJ 2015 Jun 16; 187:648. PMID: 25918178 Free PMC Article http://www.cmaj.ca/content/187/9/648
  13. Medical Knowledge Self Assessment Program (MKSAP) 19. American College of Physicians, Philadelphia 2021
  14. Sax PE Five Quick Questions from Our Course " ID in Primry Care" HIV and ID Observations. Nov 7, 2022 https://blogs.jwatch.org/hiv-id-observations/index.php/five-quick-questions-from-our-course-id-in-primary-care/2022/11/07/ - American Geriatrics Society 2015 Beers Criteria Update Expert Panel American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2015 Nov;63(11):2227-46. Epub 2015 Oct 8. PMID: 26446832 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.13702
  15. Mendez JL, Nadrous HF, Hartman TE, Ryu JH. Chronic nitrofurantoin-induced lung disease. Mayo Clin Proc. 2005 Oct;80(10):1298-302. PMID: 16212142
  16. Madani Y, Mann B. Nitrofurantoin-induced lung disease and prophylaxis of urinary tract infections. Prim Care Respir J. 2012 Sep;21(3):337-41 PMID: 22836745 PMCID: PMC6547957 Free PMC article
  17. NEJM Knowledge+