AHFS Class:

• Aminoglycosides 8:12.02

Generic Name(s):

• Neomycin Sulfate

Associated Monographs

• Aminoglycosides General Statement

Neomycin is an aminoglycoside antibiotic.1,2,14,23

Hepatic Encephalopathy

Oral neomycin is used to inhibit ammonia-forming bacteria in the GI tract as an adjunct to protein restriction and supportive therapy in patients with hepatic (portal-systemic) encephalopathy.1,2,11,13,26,27,28 The subsequent decrease in blood ammonia may result in neurologic improvement.1,2,11,27

Some clinicians recommend nonabsorbable disaccharides (lactulose) as first-line treatment to reduce blood ammonia in adults with acute hepatic encephalopathy and recommend anti-infectives (e.g., oral neomycin or metronidazole) as alternatives for treatment of acute and chronic hepatic encephalopathy.11,28 These clinicians suggest that anti-infectives be reserved for patients who have a poor response to disaccharides or do not exhibit diarrhea or acidification of the stool.11,28 It also has been suggested that oral neomycin and oral lactulose may result in additive effects11,27 and concomitant use of the drugs can be considered, if necessary, in problematic cases.11 However, other clinicians state that efficacy of nonabsorbable disaccharides and/or anti-infectives in the treatment of hepatic encephalopathy has not been adequately evaluated in controlled clinical studies and additional study is needed to more fully evaluate possible benefits and risks of such treatment.12

Perioperative Prophylaxis

Oral neomycin is used as an adjunct to mechanical cleansing of the large intestines for preoperative prophylaxis in patients undergoing colorectal surgery.2,3,6,13 For patients undergoing colorectal surgery, a regimen of oral neomycin and oral erythromycin, oral neomycin and oral metronidazole, IV cefoxitin or IV cefotetan (no longer commercially available in the US), or IV cefazolin used in conjunction with IV metronidazole usually is recommended.3,4,6 It has been suggested that an oral regimen is as effective as a parenteral regimen in patients undergoing elective colorectal surgery.3 Although many clinicians use both an oral and a parenteral regimen in patients undergoing colorectal surgery,3,4,6 there is controversy about the benefits and risks of this strategy.3,10 There is some evidence that a combined oral and parenteral regimen may be more effective than use of an oral or parenteral regimen alone;6,7,10 however, the combined regimen may be associated with a higher incidence of adverse effects (e.g., nausea, vomiting, Clostridium difficile -associated diarrhea and colitis).8,9

GI Infections

Although oral neomycin has been used as an adjunct to fluid and electrolyte replacement in the treatment of bacterial GI infections†, including diarrhea caused by enteropathogenic Escherichia coli (EPEC),13,15 the drug is no longer recommended for the treatment of any GI infections.13

Hypercholesterolemia

Oral neomycin has been used in the treatment of hypercholesterolemia†.13,16,17,20,25 The therapeutic value of the drug in hypercholesterolemia may be due in part to a reduction in GI absorption of cholesterol, resulting in enhanced elimination of cholesterol as neutral sterols in the feces.13,16,20 However, neomycin is not considered a first- or second-line agent for the treatment of hypercholesterolemia and probably should only be considered after all conventional treatments have been tried.18,25

For use of neomycin in the topical treatment of ophthalmic infections, see Neomycin 52:04.04. For use of neomycin in the topical treatment of skin infections or use as a urinary bladder irrigant, see Neomycin 84:04.04.

Administration

Neomycin sulfate is administered orally.1,2

Dosage

Potency of neomycin sulfate has been expressed both in terms of the base and the salt, but generally is expressed in terms of the sulfate.

To minimize the risk of toxicity, the lowest possible dosage and shortest duration of therapy that is effective should be used.1,2 A treatment duration longer than 2 weeks is not recommended.1,2 If treatment is prolonged, serum neomycin concentrations should be monitored to avoid potentially toxic concentrations and the benefits of the drug to the patient should be weighed against the risks of nephrotoxicity, permanent ototoxicity, and neuromuscular blockade.1

Adult Dosage

Hepatic Encephalopathy

As an adjunct in the treatment of hepatic (portal-systemic) encephalopathy, the recommended dosage of neomycin sulfate in adults with normal renal function is 4-12 g daily given in divided doses (e.g., 4 doses daily) for 5-6 days.1,2,26,28 Some clinicians recommend that adults with acute encephalopathy receive a dosage of 3-6 g daily for 1-2 weeks.11

Prior to initiation of neomycin therapy for the treatment of hepatic encephalopathy, protein should be withdrawn from the diet and use of diuretic agents avoided; protein may then be incrementally added back into the diet during treatment.1,2 Supportive therapy (including blood products) should be given as indicated.1,2

Some clinicians state that adults with chronic encephalopathy can receive oral neomycin in a dosage of 1-2 g daily.11 For the treatment of chronic hepatic insufficiency when less toxic drugs cannot be used, the manufacturers state that oral neomycin may be given in a dosage up to 4 g daily.1,2 However, patients receiving the drug for chronic hepatic insufficiency must be monitored closely for aminoglycoside toxicity.1,2,11 The risk of toxicity increases when the duration of neomycin therapy must be extended to preserve the life of a patient with hepatic encephalopathy who has failed to fully respond.1,2

Perioperative Prophylaxis

For preoperative prophylaxis in patients undergoing colorectal surgery, oral neomycin is given concomitantly with oral erythromycin or oral metronidazole and used in conjunction with an appropriate diet and catharsis.2,3,6

A minimum residue or clear liquid diet and catharsis usually is prescribed 1-3 days prior to colorectal surgery.2,3 If surgery is scheduled for 8 a.m., adults should receive 1 g of oral neomycin sulfate and 1 g of oral erythromycin base orally at 1 p.m., 2 p.m., and 11 p.m. on the day preceding surgery.2,3,6 Alternatively, adults can receive 2 g of oral neomycin sulfate and 2 g of oral metronidazole at 7 p.m. and 11 p.m. on the day preceding surgery.3

Hypercholesterolemia

For the treatment of hypercholesterolemia† when conventional treatments could not be used, adults have received oral neomycin sulfate in a dosage of 0.5-2 g daily.16,25 Neomycin should not be used for long-term treatment of hypercholesterolemia.13

Pediatric Dosage

General Pediatric Dosage

Safety and efficacy of oral neomycin in children younger than 18 years of age† have not been established.1,2 The manufacturers state that if use of neomycin is considered necessary in this age group, the drug should be used with caution and the duration of therapy should not exceed 3 weeks.1,2

The American Academy of Pediatrics (AAP) states that neonates up to 1 month of age† may receive oral neomycin in a dosage of 25 mg/kg every 6 hours and children older than 1 month of age† may receive 100 mg/kg daily given in 4 equally divided doses.5

Hepatic Encephalopathy

As an adjunct in the treatment of hepatic encephalopathy, some clinicians state that children may receive oral neomycin in a dosage of 100 mg/kg daily given in 4 divided doses for a maximum of 7 days.27

Dosage in Renal Impairment

Dosage of neomycin sulfate should be reduced or the drug discontinued in patients with renal impairment.1 Some clinicians recommend the neomycin doses be given every 6 hours in patients with glomerular filtration rates (GFRs) greater than 50 mL/minute, every 12-18 hours in those with GFRs 10-50 mL/minute, and every 18-24 hours in those with GFRs less than 10 mL/minute.24

Pharmacokinetics

Absorption

Neomycin is poorly absorbed from the GI tract.26,29 Approximately 3% of an oral dose of neomycin sulfate is absorbed from the normal GI tract.1,2,21,22 Limited evidence indicates absorption of neomycin from a retention enema is similar to that following oral administration.22,29 Absorption may be increased if mucosa is damaged or inflamed.29

In one study in adults with normal renal function, a single 4-g oral dose of neomycin sulfate produced peak plasma neomycin concentrations of 2.5-6.1 mcg/mL 1-4 hours after the dose in most patients; low plasma concentrations of the drug were detectable at 8 hours but the drug was undetectable at 24 hours.21

In adults who received 1-g doses of oral neomycin sulfate and 1-g doses of oral erythromycin at 19, 18, and 9 hours before colorectal surgery, mean peak serum concentrations of neomycin were 0.59 mcg/mL and were attained 12 hours after the first dose (i.e., 2 hours after the third dose).19

Following oral administration of neomycin sulfate, growth of most susceptible intestinal bacteria is rapidly suppressed and such suppression persists for 48-72 hours.1,2

Distribution

Following oral administration, low concentrations of neomycin are attained in intestinal wall and muscles.19

Neomycin is distributed into milk in animals; it is not known whether the drug is distributed into human milk following oral administration.1,2

Elimination

The plasma elimination half-life of neomycin usually is 2-3 hours in adults with normal renal function23,24,29 and has been reported to be 12-24 hours in adults with severe renal impairment.24

Following oral administration in adults, unabsorbed neomycin (about 97% of a dose) is excreted unchanged in feces1,13,26 and approximately 1% of the dose is excreted in urine by glomerular filtration within 24 hours.13,21,22

Chemistry and Stability

Chemistry

Neomycin is an aminoglycoside antibiotic obtained from cultures of Streptomyces fradiae .1,2,14,23 Neomycin is a mixture of neomycin A (neamine), neomycin B, and neomycin C.29 The commercially available drug is comprised almost entirely of the sulfate salt of neomycin B.29

Neomycin sulfate occurs as a white to slightly yellow, hygroscopic powder or cryodesiccated solid and is freely soluble in water and very slightly soluble in alcohol.14 Commercially available neomycin sulfate oral solution is a clear, orange solution containing 125 mg of neomycin sulfate (87.5 mg of neomycin) per 5 mL.1 Potency of neomycin sulfate has been expressed in terms of the sulfate and in terms of the base.14 Each 500 mg of neomycin sulfate is equivalent to 350 mg of neomycin.1,2

Stability

Neomycin sulfate oral solution should be stored at 15-30°C.1 Neomycin sulfate tablets should be stored in tight containers at 20-25°C.2

Additional Information

For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, and dosage and administration of neomycin, see the Aminoglycosides General Statement 8:12.02. For topical uses of neomycin, see Neomycin 52:04.04 and see 84:04.04. The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

1. Pharma-Tek Inc. Neo-Fradin^® (neomycin sulfate) oral solution prescribing information. Huntington, NY. 2002 Jul.

2. Teva. Neomycin sulfate tablets USP prescribing information. Sellersville, PA. 2003 Mar.

3. Anon. Antimicrobial prophylaxis for surgery. Med Lett Treat Guid . 2004; 2:27-32.

4. Nichols RL, Smith JW, Garcia RY et al. Current practices of preoperative bowel preparation among North American colorectal surgeons. Clin Infect Dis . 1997; 24:609-19. [PubMed 9145734]

5. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006:751, 753.

6. Bratzler DW, Houck PM, for the Surgical Infection Prevention Guidelines Writers Workgroup. antimicrobial prophylaxis for surgery: an advisory statement from the national surgical infection prevention project. Clin Infect Dis . 2004; 38:1706-15. [PubMed 15227616]

7. Schoetz DJ, Roberts PL, Murray JJ et al. Addition of parenteral cefoxitin to regimen of oral antibiotics for elective colorectal operations. Ann Surg . 1990; 212:209-12. [PubMed 2100983][PubMedCentral]

8. Espin-Basany E, Sanchez-Garcia JL, Lopez-Cano M et al. Prospective, randomized study on antibiotic prophylaxis in colorectal surgery. Is it really necessary to use oral antibiotics? Int J Colorectal Dis . 2005; 20:542-6.

9. Wren SM, Ahmed N, Jamal A et al. Preoperative oral antibiotics in colorectal surgery increase the rate of Clostridium difficile colitis. Arch Surg . 2005; 140:752-6. [PubMed 16103284]

10. Lewis RT. Oral versus systemic antibiotic prophylaxis in elective colon surgery: a randomized study and meta-analysis send a message from the 1990s. Can J Surg . 2002; 45:173-80. [PubMed 12067168][PubMedCentral]

11. Blei AT, Cordoba J, the Practice Parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy. Am J Gastroenterol . 2001; 96:1968-76. [PubMed 11467622]

12. Als-Nielsen B, Gluud LL, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy (review). Cochrane Database Syst Rev . 2004; 2:CD003044.

13. Kucers A, Crowe S, Grayson ML et al, eds. The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; 1997: 533-41.

14. The United States pharmacopoeia, 29th rev, and The national formulary, 24th ed. Rockville, MD: The United States Pharmacopeial Convention; 2005:1491-3,3217.

15. Nelson JD. Duration of neomycin for enteropathogenic Escherichia coli diarrheal disease: a comparative study of 113 cases. Pediatrics . 1971; 48:248-58. [PubMed 5560618]

16. Samuel P. Treatment of hypercholesterolemia with neomycin-a time for reappraisal. N Engl J Med . 1979; 301:595-7. [PubMed 381924]

17. Gylling H, Miettinen TA. The effect of cholesterol absorption inhibition on low density lipoprotein cholesterol level. Atherosclerosis . 1995; 117:305-8. [PubMed 8801876]

18. Meisel S, Rate R. Neomycin for hypercholesterolemia. N Engl J Med . 1980; 302:233. [PubMed 7350468]

19. DiPiro JT, Patrias JM, Townsend RJ et al. Oral neomycin sulfate and erythromycin base before colon surgery: a comparison of serum and tissue concentrations. Pharmacotherapy . 1985; 5:91-4. [PubMed 4000983]

20. Sedaghat A, Samuel P, Crouse JR et al. Effects of neomycin on absorption, synthesis, and/or flux of cholesterol in man. J Clin Invest . 1975; 55:12-21. [PubMed 1109175][PubMedCentral]

21. Kunin CM, Chalmers TC, Leevy CM et al. Absorption of orally administered neomycin and kanamycin with special reference to patients with severe hepatic and renal disease. N Engl J Med . 1960; 262:380-5. [PubMed 14412744]

22. Breen KJ, Bryant RE, Levinson JD et al. Neomycin absorption in man. Studies of oral and enema administration and effect of intestinal ulceration. Ann Intern Med . 1972; 76:211-8. [PubMed 5009591]

23. Barza M, Scheife RT. Drug therapy reviews: antimicrobial spectrum, pharmacology and therapeutic use of antibiotics, part 4: aminoglycosides. Am J Hosp Pharm . 1977; 34:723-37. [PubMed 407790]

24. Bennett WM, Muther RS, Parker RA et al. Drug therapy in renal failure: dosing guidelines for adults. Ann Intern Med . 1980; 93:62-89. [PubMed 6994534]

25. Hritcko P, Kapadia VK, Folstad J. Treatment of hypercholesterolemia with oral neomycin. AJHP . 1999; 56:2227-9. [PubMed 10565703]

26. Chambers HF. Aminoglycosides. In: Brunton LL, Lazo JS, Parker KL et al, eds. Goodman and Gillman's the pharmacological basis of therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006:1155-71.

27. Debray D, Yousef N, Durand P. New management options for end-stage chronic liver disease and acute liver failure. Pediatr Drugs . 2006; 8:1-13.

28. Harrison's principles of internal medicine. 16th ed. Kasper DL, Braunwald E, Fauci AS et al, eds. New York: McGraw-Hill; 2006.

29. Sweetman S, ed. Martindale: the complete drug reference. London: Pharmaceutical Press. Electronic version. 2006.