Neo-Rx

Administration

Oral Administration

Administer orally.1 2

Dosage

Available as neomycin sulfate; dosage expressed in terms of the sulfate.a

To minimize risk of toxicity, use lowest possible dosage and shortest duration of therapy.1 2 Closely monitor patients for aminoglycoside toxicity, especially when used for adjunctive treatment of chronic hepatic insufficiency.1 2 11

Treatment duration >2 weeks is not recommended.1 2 Weigh risks of nephrotoxicity, permanent ototoxicity, and neuromuscular blockade against benefits of prolonged treatment.1 If treatment is prolonged, closely monitor serum neomycin concentrations and renal, auditory, and vestibular functions.1

Individualize dosage taking into consideration the patient’s pretreatment body weight, renal status, and serum concentrations of the drug.b Because of potential toxicity, fixed-dosage recommendations that are not based on patient weight or serum drug concentrations are not advised.b

Pediatric Patients

Neonates ≤1 month of age†: AAP recommends 25 mg/kg every 6 hours.5

Infants and children >1 month of age†: AAP recommends 100 mg/kg daily given in 4 equally divided doses.5

Manufacturers state that if neomycin is considered necessary in children <18 years of age†, duration of therapy should not exceed 2 weeks1 2 . (See Pediatric Use under Cautions.)

Children†: 100 mg/kg daily given in 4 divided doses for ≤7 days.27

Prior to initiation of neomycin, withdraw protein from the diet and avoid diuretics; incrementally return protein back to the diet during treatment.1 2 Monitor closely;1 2 11 give supportive therapy (including blood products) as indicated.1 2

Adults

Hepatic coma: 4–12 g daily given in divided doses (e.g., 4 doses daily) for 5–6 days recommended by the manufacturers and others.1 2 26 28

Chronic hepatic insufficiency when less toxic drugs cannot be used: Up to 4 g daily recommended by the manufacturers.1 2

Some clinicians recommend 3–6 g daily for 1–2 weeks for acute encephalopathy11 and 1–2 g daily for chronic encephalopathy.11

Prior to initiation of neomycin, withdraw protein from the diet and avoid diuretics; incrementally return protein back to the diet during treatment.1 2 Monitor closely;1 2 11 give supportive therapy (including blood products) as indicated.1 2

For 8 a.m. surgery: Give 1 g neomycin sulfate and 1 g erythromycin base at 1 p.m., 2 p.m., and 11 p.m. on the day preceding surgery.2 3 6 Alternatively, give 2 g neomycin sulfate and 2 g metronidazole at 7 p.m. and 11 p.m. on the day preceding surgery.3

Begin a minimum residue or clear liquid diet 1–3 days before colorectal surgery with appropriate catharsis.2 3 6

0.5–2 g daily.16 25 Do not use for long-term treatment.13

Prescribing Limits

Adults

Maximum: 4 g daily.1 2

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time other than those for patients with hepatic encephalopathy.1 2 a

Renal Impairment

Reduce dosage or discontinue drug in patients with renal impairment.1

Some clinicians recommend that doses be given every 6 hours in those with GFR >50 mL/minute, every 12–18 hours in those with GFR 10–50 mL/minute, or every 18–24 hours in those with GFR <10 mL/minute.24

Geriatric Patients

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.1 2

Contraindications

• History of hypersensitivity or serious toxic reactions to neomycin or other aminoglycosides.1 2

• Intestinal obstruction.1 2

• Inflammatory or ulcerative GI disease; may enhance GI absorption of neomycin.1 2

Warnings/Precautions

Warnings

Patients receiving aminoglycosides should be under close clinical observation because of possible ototoxicity.1 2

Vestibular and permanent bilateral auditory ototoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other ototoxic drugs, and those who receive high dosages or prolonged treatment.1 2

Perform serial, vestibular, and audiometric tests, if feasible, in patients old enough to be tested, particularly in high-risk patients.1 2

Perform tests of the vestibulocochlearis nerve (eighth cranial nerve) function prior to and periodically during neomycin therapy.1 2

Numbness, skin tingling, muscle twitching, and convulsions also may be signs of neurotoxicity.1 2

Risk of hearing loss continues after drug withdrawal.1 2

Some aminoglycosides have caused fetal ototoxicity when administered to pregnant women.1 2 (See Pregnancy under Cautions.)

Patients receiving aminoglycosides should be under close clinical observation because of possible nephrotoxicity.1 2 Renal function should be assessed prior to therapy and daily, or more frequently, during therapy.1 2

Nephrotoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other nephrotoxic drugs, and those who receive high dosage or prolonged treatment.1 2

Monitor urine for increased protein excretion, decreased specific gravity, and the presence of cells and casts.1 2 Obtain Clcr, Scr, and/or BUN at the onset of therapy and periodically during therapy.1 2

Decrease dosage or discontinue drug if renal insufficiency develops.1 2

Neuromuscular blockade and respiratory paralysis reported following oral neomycin.1 2

Possibility of neuromuscular blockade should be considered, especially in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in those receiving massive transfusions of citrate-anticoagulated blood.1 2

Calcium salts may reverse neuromuscular blockade, but mechanical respiratory assistance may be necessary.1 2

Sensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with aminoglycosides.

Cross-sensitivity occurs among the aminoglycosides.1 2

General Precautions

To reduce development of drug-resistant bacteria and maintain effectiveness of neomycin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.2

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.2 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.2

Quickly and almost totally absorbed from body surfaces (except the urinary bladder) after local irrigation or intraoperative topical application in association with medical procedures; neurotoxicity, nephrotoxicity, neuromuscular blockade, or respiratory paralysis may occur, even with minute quantities of neomycin, regardless of renal function.1 2

Use with caution in patients with neuromuscular disorders such as myasthenia gravis or parkinsonism; may aggravate muscle weakness because of potential curare-like effect on the neuromuscular junction.1 2

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 2 Institute appropriate therapy if superinfection occurs.1 2

May produce a malabsorption syndrome for a variety of substances including fat, nitrogen, cholesterol, carotene, glucose, xylose, lactose, sodium, calcium, cyanocobalamin, and iron.1 2 Usually reversible and dose-related; occurs most frequently in prolonged therapy or at high dosage (i.e., 12 g daily).1 2 13 23

Specific Populations

Category D.1 2

Possibility of fetal harm if administered to a pregnant woman.1 2 Complete, irreversible, bilateral congenital deafness reported when another aminoglycoside (i.e., streptomycin) was used during pregnancy.1 2

IM neomycin is distributed into milk in cows; not known whether distributed into human milk.1 2 Discontinue nursing or the drug.1 2

Safety and efficacy not established in children <18 years of age.1 2

If neomycin is considered necessary in children <18 years of age†, use with caution 1 2 and do not treat for >2 weeks1 2 since GI absorption may occur.1 2

Risk of toxicity is increased in premature infants and neonates†.1 2

Increased risk of toxicity; use with caution and closely monitor renal function.1 2

When assessing renal function in geriatric patients, Clcr may be more useful than BUN or Scr.1 2

Patients with renal impairment are at higher risk of nephrotoxicity and ototoxicity.1 2

Patients with renal insufficiency may develop toxic blood concentrations unless doses are properly regulated.1 2

Common Adverse Effects

Nausea,1 2 vomiting,1 2 diarrhea,1 2 abdominal cramps.13 23

Neurotoxic, Ototoxic, or Nephrotoxic Drugs

Concomitant or sequential use with other drugs that have neurotoxic, ototoxic, or nephrotoxic effects may result in additive toxicity and should be avoided, if possible.1 2

Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, do not use concurrently with potent diuretics.1 2

Specific Drugs

Absorption

Bioavailability

Poorly absorbed from the GI tract;26 29 about 3% of an oral dose is absorbed.1 2 21 22 Damaged or inflamed mucosa may increase GI absorption.29

Rapidly and almost totally absorbed from body surfaces (except the urinary bladder) after local irrigation or intraoperative topical application in association with medical procedures.1 2

Plasma Concentrations

In adults, a single 4-g oral dose produced peak plasma concentrations of 2.5–6.1 mcg/mL at 1–4 hours after the dose.21

Distribution

Extent

Distributed in low concentrations in intestinal wall and muscles.19

Distributed into milk in animals; not known whether distributed into human milk.1 2

Plasma Protein Binding

0–30%.1 2

Elimination

Elimination Route

Excreted principally in feces (97%) as unchanged drug1 2 13 26 and in urine (1%).13 21 22

Removed by hemodialysis.1 2

Half-life

Adults with normal renal function: 2–3 hours.23 24 29

Severe renal impairment: 12–24 hours.24

Applies to neomycin: compounding powder, oral solution, oral tablet

General

Since oral neomycin is absorbed systemically after oral administration, its use may result in nephrotoxicity, neurotoxicity and/or ototoxicity, even at recommended doses and in patients with normal renal function.[Ref]

Renal

The major renal side effect of oral neomycin is nephrotoxicity, which has occurred even at recommended doses and in patients with normal renal function.[Ref]

Early signs of nephropathy include mild proteinuria, sloughing of renal tubular epithelial cells, formation of cellular casts, and decreases in creatinine clearance. Often there is a high output renal failure where daily urine volume may appear unchanged until significant increases in serum creatinine and BUN levels occur.

Neomycin damages renal tubules by causing tubular epithelial cell necrosis. It is considered the most nephrotoxic aminoglycoside.[Ref]

Nervous system

Early symptoms of neomycin-induced auditory toxicity may manifest as high tone hearing loss, tinnitus, or a feeling of fullness in the ear, or its onset may be asymptomatic. If ototoxicity occurs, the onset of hearing loss is between several days to 6 weeks after therapy begins; however, it may not occur for months or years after neomycin has been discontinued. Symptoms of vestibulotoxicity may include tinnitus, vertigo and ataxia.

Neomycin is considered more ototoxic than vestibulotoxic. It progressively accumulates in the inner ear and which leads to sensory hair cell loss in the in the cochlea and damage to the stria vascularis. In an animal study, neomycin was found to be more ototoxic than gentamicin, kanamycin and dihydrostreptomycin.

One case report series describes 5 cases of hearing impairment associated with long-term oral neomycin therapy for hepatic encephalopathy. Doses ranged from 2 to 12 g/day and were administered for 8 to 28 months; in 2 cases paromomycin was also administered. Renal failure did not occur.[Ref]

Nervous system side effects associated with oral neomycin therapy have included neuromuscular blockade, respiratory paralysis, and eighth cranial nerve damage with hearing loss, even at recommended doses and in patients with normal renal function. Symptoms of neurotoxicity include numbness, tingling, muscle twitching, and convulsions.[Ref]

Other

Oral neomycin therapy may result in overgrowth of nonsusceptible organisms, especially fungi.[Ref]

A case of fatal Candida albicans pyelonephritis and septicemia following preoperative bowel preparation with oral neomycin and bacitracin has been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects most commonly include nausea, vomiting and diarrhea. Clostridium difficile colitis has also been reported with oral neomycin therapy.[Ref]

Some side effects of neomycin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

1 g orally every hour for 4 doses followed by 1 g every 4 hours for 5 doses

Alternate dosing: 6 g/day orally divided every 4 hours for 2 to 3 days

3 g/day orally in 4 divided doses

The safety and efficacy of neomycin in children less than 18 years of age has not been established. However, the use of neomycin may be appropriate is some situations.

Less than 1 month: 50 mg/kg/day orally divided every 6 hours
1 year to 18 years: 50 to 100 mg/kg/day orally divided every 6 hours