NEOMYCIN SULFATE AND POLYMYXIN B SULFATE GRAMICIDIN
Clinical safety rating: safe
Other nephrotoxic or ototoxic drugs increase risk of toxicity Can cause ototoxicity and nephrotoxicity with systemic use.
Neomycin is an aminoglycoside antibiotic that binds to the 30S ribosomal subunit, inhibiting bacterial protein synthesis. Polymyxin B is a polypeptide antibiotic that disrupts bacterial cell membrane permeability by interacting with phospholipids. Gramicidin is a polypeptide antibiotic that increases cell membrane permeability by forming ion channels, leading to bacterial cell death.
| Metabolism | Neomycin is minimally absorbed after topical application and is excreted unchanged in the urine. Polymyxin B is not significantly absorbed. Gramicidin is not systemically absorbed. |
| Excretion | Renal: ~95% for neomycin (unchanged), minimal for polymyxin B (1-10% unchanged) and gramicidin (<1%). Fecal: 50-60% for polymyxin B (biliary), ~1% for neomycin. |
| Half-life | Neomycin: 2-3 hours (normal renal function); polymyxin B: 6-8 hours; gramicidin: ~10 hours (estimated from topical absorption). Prolonged in renal impairment, especially for polymyxin B. |
| Protein binding | Neomycin: 0-30% (low); polymyxin B: 80-90% (alpha-1-acid glycoprotein, albumin); gramicidin: 50-70% (albumin). |
| Volume of Distribution | Neomycin: 0.25-0.4 L/kg (extracellular water); polymyxin B: 0.3-0.6 L/kg (limited tissue penetration); gramicidin: 0.5-0.8 L/kg (estimated, based on topical data). |
| Bioavailability | Oral: <3% for neomycin and polymyxin B (<1% for gramicidin); topical/ophthalmic/otic: 100% (local). No IV formulation. |
| Onset of Action | Topical ophthalmic: 15-30 minutes; otic: 24-48 hours for full effect; topical dermatological: 2-3 days for improvement. |
| Duration of Action | Ophthalmic: 4-6 hours between doses; otic: sustained with q.i.d. dosing; topical dermatological: 12-24 hours after application. |
| Molecular Weight | Neomycin sulfate: ~908.9 Da (complex); Polymyxin B sulfate: ~1301.9 Da; Gramicidin: ~1882.3 Da (mixture). Average composite: varied. |
Instill 2 drops (or appropriate amount) into affected eye(s) every 2-4 hours for 7-10 days. Frequency may be increased to every 1-2 hours in severe infections. Ophthalmic suspension, not for injection.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No systemic absorption; renal adjustment not required. |
| Liver impairment | No systemic absorption; hepatic adjustment not required. |
| Pediatric use | Same as adult dosing; 1-2 drops into affected eye(s) every 2-4 hours. Use with caution in neonates due to potential for systemic absorption through ocular mucosa. |
| Geriatric use | Same as adult dosing; no specific adjustments needed. Monitor for local adverse effects. |
| 1st trimester | Avoid. Aminoglycosides cross the placenta; risk of fetal nephrotoxicity and ototoxicity. Gramicidin may cause hemolysis. |
| 2nd trimester | Avoid. Theoretical risks similar to T1; use only if clearly needed and no safer alternative. |
| 3rd trimester | Avoid. Potential for fetal auditory and renal toxicity, especially with prolonged use. |
Clinical note
Other nephrotoxic or ototoxic drugs increase risk of toxicity Can cause ototoxicity and nephrotoxicity with systemic use.
| FDA category | Animal |
| Placental transfer | Aminoglycosides (neomycin) cross placenta; polymyxin B and gramicidin have limited data but likely minimal transfer due to high molecular weight. Neomycin: 20-30% of maternal serum levels in fetal serum. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Common Effects | topical infections |
| Serious Effects |
Hypersensitivity to any componentMyasthenia gravis (risk of neuromuscular blockade)Preexisting auditory or renal impairment (if systemic absorption possible)
| Precautions | Prolonged use may result in overgrowth of nonsusceptible organisms including fungi, Potential for ototoxicity and nephrotoxicity if applied to large areas or broken skin, Hypersensitivity reactions, Cross-sensitivity with other aminoglycosides |
| Food/Dietary | No clinically relevant food interactions. |
Loading safety data…
| Neomycin and polymyxin B are poorly absorbed orally; gramicidin is not absorbed. Systemic levels in infant expected to be negligible. However, due to risk of alteration of infant gut flora and potential for hypersensitivity, caution advised. Use only if benefit outweighs risk. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Neomycin sulfate, polymyxin B sulfate, and gramicidin are poorly absorbed via topical/ophthalmic/otic routes; systemic exposure is negligible. No adequate and well-controlled studies in pregnant women. Animal reproduction studies for the combination are lacking. However, topical aminoglycosides are not associated with increased risk of congenital anomalies. Fetal risk is considered minimal when used as directed. Avoid use for extended periods or on large areas of broken skin. |
| Fetal Monitoring | No specific monitoring required beyond routine prenatal care due to negligible systemic absorption. Observe for signs of skin irritation or allergic reaction at application site. |
| Fertility Effects | No data exist on effects of topical neomycin/polymyxin B/gramicidin on fertility. Systemic aminoglycosides may cause testicular damage in animals; relevance to topical use is unknown. |
| Clinical Pearls | This combination (neomycin/polymyxin B/gramicidin) is used for otic or ophthalmic topical infections. Avoid in patients with tympanic membrane perforation (otic use) due to risk of ototoxicity. Neomycin carries risk of sensitization; discontinue if allergic reaction (e.g., redness, swelling) occurs. Gramicidin is not absorbed systemically, minimizing systemic toxicity. Prolonged use may lead to overgrowth of resistant organisms. |
| Patient Advice | Use exactly as prescribed; do not use longer than recommended to avoid sensitization or superinfection. · For otic use: do not use if you have a perforated eardrum or ear tube, as it may cause hearing loss. · Wash hands before and after application; avoid contaminating the dropper tip. · If you develop rash, itching, or swelling at the application site, stop use and inform your doctor. · Do not use for eye infections unless specifically prescribed for ophthalmic use; even then, avoid touching eye with dropper. |