neomycin

Aminoglycoside Antibiotics

May be administered without regard to meals.

Topical formulations are not for ophthalmic use.
Rub cream or ointment gently into cleansed affected area. Care should be taken to avoid further contamination of the infected skin.
Treated area may be covered with sterile gauze if desired.

seizures / Delayed / Incidence not known
ototoxicity / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
nephrotoxicity / Delayed / Incidence not known
hyposthenuria / Delayed / Incidence not known
renal tubular acidosis (RTA) / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known

neurotoxicity / Early / Incidence not known
myasthenia / Delayed / Incidence not known
pyuria / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
iron deficiency / Delayed / Incidence not known
vitamin D deficiency / Delayed / Incidence not known
vitamin B12 deficiency / Delayed / Incidence not known
folate deficiency / Delayed / Incidence not known

vertigo / Early / Incidence not known
tinnitus / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
cylindruria / Delayed / Incidence not known
steatorrhea / Delayed / Incidence not known
nausea / Early / Incidence not known
vomiting / Early / Incidence not known
diarrhea / Early / Incidence not known
vitamin B6 deficiency / Delayed / Incidence not known

Neomycin is an aminoglycoside and is absorbed systemically after oral administration; toxic reactions may occur. Closely monitor patients receiving systemically absorbed aminoglycosides, such as neomycin, for nephrotoxicity. Assess creatinine clearance (CrCl) in all patients before therapy and daily during therapy, particularly in those at increased risk of nephrotoxicity. In patients with pre-existing renal impairment, renal failure, or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe nephrotoxic adverse reactions are sharply increased. Renal failure has been reported after irrigation of both small and large surgical fields with minute quantities of neomycin. Advanced age, dehydration, and those receiving concomitant nephrotoxic medications have a higher risk. Avoid concurrent and/or sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic because toxicity may be additive. In the setting of worsening renal function, assess the benefit of continuing neomycin therapy. Aminoglycosides are associated with major toxic effects on renal tubules. Hemodialysis may aid in removal in the event of overdose or toxic reactions, especially if renal function is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity is usually reversible.

Neomycin is an aminoglycoside and is absorbed systemically after oral administration; toxic reactions may occur. Monitor patients receiving systemically absorbed aminoglycosides, such as neomycin, for neurotoxicity, including ototoxicity and hearing impairment. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. Consider serial audiograms for high-risk patients. The risk of hearing loss increases with the degree of exposure (high or prolonged therapy), pre-existing renal impairment, concomitant or sequential nephrotoxic or ototoxic agents, dehydration, and advanced age. Patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly in the m.1555A>G variant, may develop ototoxicity even when aminoglycoside serum concentrations are within the recommended range. These variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity, including severe cases, is unknown. If there is a known maternal history of ototoxicity due to aminoglycosides or a known mitochondrial DNA variant, consider alternative treatments unless the severity of the infection and lack of alternatives outweighs the risk of permanent hearing loss. Discontinue therapy if there is evidence of auditory or vestibular toxicity. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Delayed-onset irreversible deafness has been reported after irrigation of both small and large surgical fields with minute quantities of neomycin. Auditory changes are irreversible, usually bilateral, and may be partial or total. Symptoms of ototoxicity can include dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss and may manifest during therapy or after discontinuation. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions.

Aminoglycosides, like neomycin, are associated with neuromuscular blockade and may cause severe neuromuscular weakness lasting hours to days. Respiratory paralysis, respiratory insufficiency, or respiratory depression may occur when aminoglycosides are instilled intraperitoneally concomitantly with anesthesia and muscle-relaxing drugs. Neuromuscular blockade has also been reported with both oral and parenteral use of aminoglycosides. Neuromuscular blockage and respiratory paralysis have been reported following the oral use of neomycin. Delayed-onset death due to neuromuscular blockade (regardless of the status of renal function) have been reported following irrigation of both small and large surgical fields with minute quantities of neomycin. Clinicians should be aware of the possibility of neuromuscular blockade and respiratory paralysis if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood). If neuromuscular blockade occurs, calcium salts may reduce these effects, but mechanical respiratory assistance may be needed. Aminoglycosides may aggravate muscle weakness in patients with neuromuscular disease such as myasthenia gravis, botulism, or parkinsonism.

Neo-Fradin

Rx

Aminoglycoside antibiotic derived
Used for preoperative bowel preparation for colorectal surgery and for adjunctive treatment of hepatic encephalopathy or hepatic coma
Oral bioavailability is poor, but systemic side effects may occur

1 g PO in combination with metronidazole or erythromycin for 3 doses given over 10 hours beginning the afternoon and evening prior to the surgery. Intravenous antibmicrobial prophylaxis should also be given prior to the surgical incision.

15 mg/kg/dose (Max: 1 g/dose) PO in combination with metronidazole or erythromycin for 3 doses given over 10 hours beginning the afternoon and evening prior to the surgery. Intravenous antibmicrobial prophylaxis should also be given prior to the surgical incision.

4 to 12 g/day PO in divided doses for 5 to 6 days; doses up to 4 g/day PO may be used chronically if necessary.

100 mg/kg/day PO in 4 divided doses for up to 7 days.

500 mg PO twice daily for 7 to 10 days.

100 mg/kg/day (Max: 1,000 mg/day) PO in 4 divided doses for 7 to 10 days.

†Indicates off-label use

No dosage adjustment required. Use aminoglycosides with caution in patients with severe hepatic disease (cirrhosis), as use may precipitate hepato-renal syndrome.

Dosage should be modified depending on clinical response and degree of renal impairment, but no quantitative recommendations are available.

Alpha-glucosidase Inhibitors: (Minor) Neomycin increased the unpleasant gastrointestinal side-effects of acarbose. A similar reaction may be expected with miglitol. If such adverse effects are severe, the dosage of miglitol can be reduced during neomycin treatment.
Amphotericin B lipid complex (ABLC): (Minor) Because the systemic absorption of neomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of amphotericin B and systemic neomycin may increase the risk of nephrotoxicity or ototoxicity. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B liposomal (LAmB): (Minor) Because the systemic absorption of neomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of amphotericin B and systemic neomycin may increase the risk of nephrotoxicity or ototoxicity. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Amphotericin B: (Minor) Because the systemic absorption of neomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of amphotericin B and systemic neomycin may increase the risk of nephrotoxicity or ototoxicity. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as aminoglycosides (particularly kanamycin, streptomycin, and neomycin). Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, with aminoglycosides may have additive nephrotoxic potential.
Beractant: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation.
Botulinum Toxins: (Minor) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. However, neomycin oral and topical products are not well absorbed systemically; interactions are not expected.
Calfactant: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation.
Cisplatin: (Major) Avoid the concurrent and/or sequential use of systemic neomycin with cisplatin due to the risk of additive nephrotoxicity and ototoxicity. Both drugs can cause nephrotoxicity and ototoxicity, which may be additive when used together.
Clindamycin: (Moderate) Concomitant use of neomycin and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Major) Avoid the concurrent and/or sequential use of neomycin and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity.
Cyanocobalamin, Vitamin B12: (Minor) Oral neomycin has been shown to inhibit the gastrointestinal absorption of cyanocobalamin, Vitamin B12. Caution is warranted with concomitant use.
Cyclosporine: (Minor) Because the systemic absorption of neomycin is minimal, the risk of this interaction is expected to be low; however, the combined use of cyclosporine and systemic neomycin may increase the risk of nephrotoxicity or ototoxicity.
Dienogest; Estradiol valerate: (Moderate) Anti-infectives that disrupt the normal GI flora, including neomycin, may potentially decrease the effectiveness of estrogen-containing oral contraceptives.
Digoxin: (Moderate) Large doses of neomycin have been reported to reduce the absorption of digoxin leading to reduced steady-state digoxin concentrations of 28%. It is thought that the decrease in digoxin absorption is due to alterations in the properties of the gut wall. Therefore, separating the time of administration between these drugs and digoxin will probably not reduce the potential interaction. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of neomycin. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Estradiol: (Moderate) Anti-infectives that disrupt the normal GI flora, including neomycin, may potentially decrease the effectiveness of estrogen-containing oral contraceptives. (Moderate) Anti-infectives which disrupt the normal GI flora, including neomycin, may potentially decrease the effectiveness of estrogen containing oral contraceptives. Alternative or additional contraception may be advisable.
Fluorouracil, 5-FU: (Moderate) Oral neomycin has been shown to inhibit the gastrointestinal absorption of fluorouracil, 5-FU. Caution is warranted with concomitant use.
Lactulose: (Moderate) Antibiotics that reduce colonic flora theoretically interfere with the biological conversion of lactulose to its active, acidic products. Since neomycin is also used in the treatment of hepatic encephalopathy, concomitant use may interfere with the effectiveness of lactulose. Patients taking both drugs concurrently should be monitored for the possibility of a decreased response to lactulose.
Methotrexate: (Moderate) Oral neomycin has been shown to inhibit the gastrointestinal absorption of methotrexate. Caution is warranted with concomitant use.
Nonsteroidal antiinflammatory drugs: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, such as aminoglycosides.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Penicillin V: (Minor) Oral neomycin has been shown to reduce the bioavailability of oral penicillin V.
Poractant Alfa: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation.
Regorafenib: (Moderate) Monitor for a decrease in the efficacy of regorafenib if coadministration with neomycin is necessary. Coadministration with neomycin, a non-absorbable antibiotic, did not have a clinically meaningful effect on the mean AUC of single-dose regorafenib in 27 healthy mean; however, the mean AUC of active metabolites M-2 and M-5 decreased by 76% and 86%, respectively.
Sorafenib: (Moderate) Monitor for decreased clinical response to sorafenib if coadministration with neomycin is necessary. Concomitant administration of oral neomycin and sorafenib decreased the AUC of sorafenib by 54% in healthy volunteers who first received neomycin 1 gm by mouth three times daily for 5 days.
Surfactants: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation.
Voclosporin: (Moderate) Concomitant use of voclosporin and neomycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Warfarin: (Moderate) Oral administration of neomycin inhibits vitamin K-synthesizing intestinal bacteria and can potentiate the effects of warfarin.

Neo-Fradin/Neomycin/Neomycin Sulfate Oral Sol: 5mL, 125mg
Neomycin/Neomycin Sulfate Oral Tab: 500mg

12 g/day PO.

12 g/day PO.

Safety and efficacy have not been established; however, doses up to 100 mg/kg/day PO have been used off-label.

Safety and efficacy have not been established; however, doses up to 100 mg/kg/day PO have been used off-label.

Safety and efficacy have not been established; however, doses up to 45 mg/kg/day PO have been used off-label.

Safety and efficacy have not been established.

Neomycin is bactericidal in action. Similar to other aminoglycosides, it inhibits bacterial protein synthesis through irreversible binding to the 30 S ribosomal subunit of susceptible bacteria. Neomycin is actively transported into the bacterial cell where it binds to receptors present on the 30 S ribosomal subunit. This binding interferes with the initiation complex between the messenger RNA (mRNA) and the subunit. As a result, abnormal, nonfunctional proteins are formed due to misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins.
 
In the adjunctive treatment of hepatic encephalopathy or coma, neomycin is used to suppress bacteria in the gut that produce urease, an enzyme that breaks down urea into carbon dioxide (CO2) and ammonia (NH3). By inhibiting the growth of urease-producing bacteria, the amount of ammonia available for absorption from the gut is decreased, resulting in decreased serum and CSF levels and clinical improvement.
 
Neomycin can form insoluble complexes with bile acids in the intestine. Small doses of neomycin reduce LDL. This mechanism of action is somewhat similar to that of the bile acid sequestrants.

Neomycin is used orally or topically. The small absorbed fraction is rapidly distributed in the tissues and excreted by the kidneys. The unabsorbed portion of neomycin (97%) is primarily excreted unchanged in feces. The amount of systemically absorbed neomycin transferred to the tissues increases cumulatively with repeated dosing with the kidneys as the primary excretory path. With repeated dosing, progressive accumulation also occurs in the inner ear. Release of tissue-bound neomycin occurs slowly over a period of several weeks after dosing has been discontinued. Protein binding is low (0% to 30%).
 
Affected cytochrome P450 isoenzymes and drug transporters: None

About 3% of an oral dose of neomycin is absorbed from the GI tract; GI obstruction can increase absorption. Growth of most intestinal bacteria is rapidly suppressed after oral administration, with suppression persisting for 48 to 72 hours.

Systemic exposure to neomycin may cause fetal harm during pregnancy. Aminoglycosides cross the placenta. There have been reports of total irreversible bilateral congenital deafness in newborns whose mothers received streptomycin, a related aminoglycoside, during pregnancy. Serious side effects to the mother, fetus, or newborn have not been reported with use of other aminoglycosides when used during pregnancy. If neomycin is used during pregnancy or if the patient becomes pregnant during treatment with neomycin, advise the mother of the potential risk to the fetus.

It is not known whether neomycin is excreted in human milk, but it has been shown to be excreted in cow milk after a single intramuscular injection. Other aminoglycosides have been shown to be excreted in human milk. Because of the potential for serious adverse reactions from aminoglycosides in nursing infants, discontinue breast-feeding or discontinue neomycin, taking into account the importance of the drug to the mother. Previous American Academy of Pediatrics (AAP) recommendations considered gentamicin, kanamycin, and streptomycin to be usually compatible with breast-feeding.