NEOMYCIN AND POLYMYXIN B SULFATES AND GRAMICIDIN
Clinical safety rating: safe
Other nephrotoxic or ototoxic drugs increase risk of toxicity Can cause ototoxicity and nephrotoxicity with systemic use.
Neomycin and gramicidin are aminoglycoside and polypeptide antibiotics, respectively, that inhibit bacterial protein synthesis by binding to the 30S and 50S ribosomal subunits, while polymyxin B is a cationic detergent that disrupts bacterial cell membrane integrity by binding to lipopolysaccharides.
| Metabolism | Neomycin: minimally metabolized, primarily renal excretion; Polymyxin B: not metabolized, primarily renal excretion; Gramicidin: not metabolized, primarily renal excretion. |
| Excretion | Neomycin and polymyxin B sulfates and gramicidin are poorly absorbed from intact skin or ophthalmic sites. After topical application, absorbed neomycin is excreted primarily unchanged in urine (30-50% of absorbed dose) via glomerular filtration; polymyxin B is excreted slowly via renal tubular secretion and glomerular filtration (60-70% of absorbed dose in urine); fecal elimination accounts for minor amounts. Gramicidin is not significantly absorbed. |
| Half-life | Neomycin: plasma half-life ~2-3 hours in patients with normal renal function, but can extend to 12-24 hours or more in renal impairment. Polymyxin B: half-life ~6 hours in normal renal function, prolonged significantly in renal failure (up to 2-3 days). Gramicidin: not systemically absorbed; half-life not applicable. |
| Protein binding | Neomycin: <10% bound to serum proteins. Polymyxin B: approximately 60% bound to serum proteins. Gramicidin: not systemically absorbed; binding not clinically relevant. |
| Volume of Distribution | Neomycin: Vd ~0.2-0.4 L/kg (limited distribution due to high polarity). Polymyxin B: Vd ~0.5-0.8 L/kg (distributes mainly in extracellular fluid). Gramicidin: not applicable. |
| Bioavailability | Topical and ophthalmic: Bioavailability is negligible (<0.1%) due to poor absorption through intact skin and mucosa. Oral: Not used systemically (highly toxic if absorbed). Intravenous: Not available. |
| Onset of Action | Ophthalmic use: Onset of antibacterial effect occurs within 1-2 hours after application. Topical dermatologic: Onset varies depending on infection severity; clinical improvement typically seen within 24-48 hours. |
| Duration of Action | Ophthalmic: Duration of activity is approximately 6-8 hours after a single dose, requiring frequent administration (every 4-6 hours). Topical: Duration depends on formulation and site; typically 12 hours after application. |
| Molecular Weight | Neomycin sulfate ~712.7 Da; Polymyxin B sulfate ~1301.5 Da; Gramicidin ~1882 Da. (Combination product: variable). |
1-2 drops or a small amount applied to affected eye(s) every 4 hours, or more frequently if severe, for up to 7-10 days. Ophthalmic ointment: apply a 1/2-inch ribbon into conjunctival sac every 3-4 hours.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dose adjustment required for topical ophthalmic use due to negligible systemic absorption. |
| Liver impairment | No dose adjustment required for topical ophthalmic use. |
| Pediatric use | Safety and efficacy in children <2 years have not been established. For children >=2 years, same as adult dosing. |
| Geriatric use | No specific dose adjustments; use with caution due to potential for prolonged healing or increased sensitivity. |
| 1st trimester | Avoid. Aminoglycosides and polymyxins cross placenta; potential for fetal ototoxicity and nephrotoxicity. Use only if clearly needed. |
| 2nd trimester | Avoid. Same risks as first trimester; use only if no alternative. |
| 3rd trimester | Avoid. Potential for neonatal toxicity, especially with prolonged use near term. |
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 limited data but likely minimal transfer due to high molecular weight. Gramicidin not systemically absorbed. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Common Effects | topical infections |
| Serious Effects |
History of hypersensitivity to any ingredientMyasthenia gravis (risk of neuromuscular blockade with polymyxins)Preexisting severe renal impairment (risk of nephrotoxicity)Otic administration if tympanic membrane perforation (risk of ototoxicity)
| Precautions | Prolonged use may result in overgrowth of nonsusceptible organisms including fungi., Hypersensitivity reactions, including contact dermatitis, may occur., Ototoxicity and nephrotoxicity risk with systemic absorption if applied to open wounds or damaged skin., Use with caution in patients with renal impairment or hearing loss. |
| Food/Dietary | No significant food interactions. Avoid alcohol as it may exacerbate dizziness if present. |
Loading safety data…
| Minimal systemic absorption after topical application. Considered unlikely to cause adverse effects in breastfed infants. However, caution with prolonged use or application to large areas. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Neomycin and polymyxin B (both poorly absorbed) and gramicidin (not absorbed) present negligible systemic exposure following topical or otic administration; no known teratogenic effects in humans. However, neomycin has been associated with ototoxicity and nephrotoxicity when absorbed systemically. Avoid use on broken skin or in large areas during pregnancy, especially first trimester. FDA Pregnancy Category C for neomycin (systemic) and D for polymyxin B (systemic); topical use considered low risk. |
| Fetal Monitoring | No specific monitoring required for topical/otic use. If used on extensive wounds or mucosal surfaces, monitor for signs of nephrotoxicity (urine output, serum creatinine) and ototoxicity (hearing loss, tinnitus). For prolonged use, consider audiometry and renal function tests. |
| Fertility Effects | No known effects on fertility from topical/otic use. Systemic neomycin may impair spermatogenesis in animal studies at high doses, but relevance to humans is unknown. |
| Clinical Pearls | Neomycin and polymyxin B sulfates and gramicidin is a combination otic suspension used for treating bacterial ear infections, typically otitis externa. Avoid use in patients with perforated tympanic membrane due to ototoxicity risk from neomycin. Monitor for hypersensitivity, especially to neomycin, which can cause contact dermatitis. Do not use for prolonged periods to prevent superinfection. |
| Patient Advice | Instill drops with the affected ear facing up and remain in that position for 5 minutes. · Do not touch the dropper tip to any surface to avoid contamination. · Complete the full course even if symptoms improve. · Stop use and consult doctor if rash, itching, or hearing changes occur. · Do not use if ear drum is perforated or if you have ear tubes. |