TERRAMYCIN W/ POLYMYXIN B SULFATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TERRAMYCIN W/ POLYMYXIN B SULFATE (TERRAMYCIN W/ POLYMYXIN B SULFATE).
Oxytetracycline: inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit, blocking aminoacyl-tRNA binding. Polymyxin B sulfate: disrupts bacterial cell membrane permeability by binding to lipopolysaccharides in Gram-negative bacteria.
| Metabolism | Oxytetracycline: undergoes minimal metabolism; primarily excreted unchanged in urine and feces. Polymyxin B sulfate: not significantly metabolized, excreted mainly unchanged in urine. |
| Excretion | Approximately 60% of oxytetracycline is excreted unchanged in the urine via glomerular filtration; 20-30% is eliminated in feces via biliary secretion. Polymyxin B is primarily eliminated by renal tubular secretion, with about 60% of a parenteral dose recovered unchanged in urine within 24 hours; minor fecal elimination. |
| Half-life | Oxytetracycline: terminal elimination half-life is 6-10 hours in patients with normal renal function; extends to 48-60 hours in severe renal impairment. Polymyxin B: terminal half-life is 6-8 hours in normal renal function; prolonged to 2-3 days in anuria. |
| Protein binding | Oxytetracycline: approximately 20-35% bound to plasma proteins, primarily albumin. Polymyxin B: approximately 50-60% bound to plasma proteins. |
| Volume of Distribution | Oxytetracycline: 1.0-1.5 L/kg, indicating extensive tissue distribution, particularly high in liver, kidney, and bone. Polymyxin B: 0.15-0.3 L/kg, reflecting limited distribution mainly to extracellular fluid. |
| Bioavailability | Oral oxytetracycline: approximately 60-80% absorbed from the gastrointestinal tract; absorption decreased by food and dairy. Polymyxin B: negligible oral absorption (<1% due to poor gastrointestinal penetration); not administered orally for systemic effect. |
| Onset of Action | Oral: oxytetracycline onset is 1-2 hours (systemic); topical: polymyxin B begins antimicrobial activity within 30-60 minutes at the site. |
| Duration of Action | Oral oxytetracycline: antimicrobial levels sustained for 6-8 hours; topical polymyxin B: local effect persists 6-12 hours after application. |
| Molecular Weight | 496.86 |
1-2 g oxytetracycline (as hydrochloride) plus 100,000-250,000 units polymyxin B sulfate IM every 8-12 hours (deep IM only); ophthalmic: 1-2 drops suspension every 4-6 hours; topical: apply thin layer to affected area 2-4 times daily.
| Dosage form | OINTMENT |
| Renal impairment | For oxytetracycline: CrCl >50 mL/min: usual dose q12h; CrCl 10-50 mL/min: usual dose q18-24h; CrCl <10 mL/min: usual dose q24h or avoid. Polymyxin B: CrCl >30 mL/min: usual dose; CrCl 20-30 mL/min: 1 mg/kg q36h; CrCl 10-20 mL/min: 1 mg/kg q48h; CrCl <10 mL/min: 1 mg/kg q72h or consider alternative. |
| Liver impairment | Oxytetracycline: Avoid in severe hepatic impairment (Child-Pugh C); reduce dose by 50% in moderate (Child-Pugh B) and monitor. Polymyxin B: No specific adjustment but caution in severe hepatic disease. |
| Pediatric use | Oxytetracycline: Contraindicated in children <8 years due to tooth discoloration. For ages >8 years: 25-50 mg/kg/day oxytetracycline IM in divided doses q8-12h. Polymyxin B: 15,000-25,000 units/kg/day IM divided q6-8h. |
| Geriatric use | Use lower end of dosing range for oxytetracycline due to age-related renal decline; monitor renal function. Polymyxin B: Adjust based on renal function; increased risk of nephrotoxicity and neurotoxicity in elderly. |
| 1st trimester | Avoid use unless no safer alternative; tetracyclines may cause fetal skeletal malformations and reversible inhibition of bone growth. |
| 2nd trimester | Avoid use unless no safer alternative; may cause permanent tooth discoloration and enamel hypoplasia if administered after the 4th month of gestation. |
| 3rd trimester | Avoid use; risk of permanent tooth discoloration and enamel hypoplasia; also associated with maternal hepatotoxicity. |
Clinical note
Comprehensive clinical and safety monograph for TERRAMYCIN W/ POLYMYXIN B SULFATE (TERRAMYCIN W/ POLYMYXIN B SULFATE).
| Placental transfer | Tetracyclines, including oxytetracycline, cross the placenta; fetal serum levels reach 60-70% of maternal levels. |
| Breastfeeding | Excreted in low concentrations into breast milk; theoretical risk of dental staining and bone growth suppression in nursing infants; use only if essential and monitor infant for gastrointestinal disturbances. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to oxytetracycline, polymyxin B sulfate, or any componentSevere renal impairment (tetracycline accumulation)Myasthenia gravis (due to polymyxin B)Porphyria (tetracyclines may exacerbate)
| Precautions | Prolonged use may result in overgrowth of nonsusceptible organisms including fungi, Sensitivity reactions may occur in patients with known hypersensitivity to tetracyclines or polymyxins, Avoid use in patients with impaired renal function (risk of nephrotoxicity from polymyxin B) |
| Food/Dietary | No clinically significant food interactions for ophthalmic use. |
| Clinical Pearls |
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| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Tetracyclines cross the placenta. First trimester: minimal risk, but associated with reversible inhibition of fetal bone growth. Second and third trimesters: risk of permanent tooth discoloration (yellow-brown) and enamel hypoplasia; also possible retardation of skeletal development. Polymyxin B has low placental transfer; no known teratogenicity. |
| Fetal Monitoring | Monitor maternal renal and hepatic function; assess fetal growth and amniotic fluid volume; dental examination of child postnatally; avoid use after 4th month of pregnancy. |
| Fertility Effects | Tetracyclines may impair male fertility by affecting sperm motility and density. No definitive human data on female fertility. Polymyxin B not associated with fertility impairment. |
| For ophthalmic use only; avoid prolonged use to prevent fungal or bacterial superinfection. Monitor for hypersensitivity reactions, especially in patients allergic to polymyxins or tetracyclines. Do not use for viral or fungal eye infections. |
| Patient Advice | Wash hands before and after applying the ointment. · Avoid touching the tube tip to the eye or any surface. · Apply a thin strip into the conjunctival sac, then close the eye gently. · Do not wear contact lenses during treatment. · Complete the full course even if symptoms improve. · May cause temporary blurred vision; avoid driving until vision clears. |