POLYTRIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for POLYTRIM (POLYTRIM).
Polymyxin B sulfate binds to the lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria, disrupting membrane integrity and causing cell death. Trimethoprim inhibits bacterial dihydrofolate reductase, blocking the conversion of dihydrofolic acid to tetrahydrofolic acid, thereby inhibiting bacterial DNA synthesis.
| Metabolism | Polymyxin B undergoes minimal systemic absorption and is primarily metabolized in the liver via unknown pathways. Trimethoprim is mainly metabolized in the liver via oxidation and glucuronidation, with CYP450 enzymes involved. |
| Excretion | Renal excretion accounts for approximately 40% of the dose as unchanged polymyxin B and 60% as unchanged trimethoprim. Biliary/fecal elimination is minimal (<5% for each component). |
| Half-life | Terminal elimination half-life of polymyxin B is 4.5-6 hours; for trimethoprim it is 8-10 hours. In renal impairment, half-life of both components is prolonged. |
| Protein binding | Polymyxin B: ~80-92% bound to plasma proteins; trimethoprim: ~42-46% bound, primarily to albumin. |
| Volume of Distribution | Polymyxin B: 0.7-1.0 L/kg; trimethoprim: 1.5-2.0 L/kg. Indicates extensive tissue penetration, including into ocular tissues. |
| Bioavailability | Ophthalmic: Systemic bioavailability is negligible (<0.1%) due to topical administration; drug acts locally in the eye. |
| Onset of Action | Ophthalmic: Clinical improvement begins within 2-3 days of starting therapy. |
| Duration of Action | Dosing interval is every 3 hours (up to 4 times daily); continuous antibacterial effect requires frequent administration due to short half-life. |
1 drop in the affected eye(s) every 4 hours for 7-10 days.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dose adjustment required for topical ophthalmic use. |
| Liver impairment | No dose adjustment required for topical ophthalmic use. |
| Pediatric use | Same as adult dose for children ≥2 months: 1 drop every 4 hours. |
| Geriatric use | Same as adult dose; no specific precautions for topical use. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for POLYTRIM (POLYTRIM).
| Breastfeeding | Trimethoprim excreted into breast milk (M/P ratio ~0.5-1.0). Polymyxin B: minimal excretion due to poor oral absorption. American Academy of Pediatrics considers trimethoprim compatible with breastfeeding. However, avoid in nursing infants with G6PD deficiency or hyperbilirubinemia. |
| Teratogenic Risk | Polymyxin B and trimethoprim combination. Trimethoprim is a folate antagonist. First trimester exposure associated with neural tube defects and cardiovascular malformations (folate antagonism). Second and third trimesters: risk of megaloblastic anemia and theoretical risk of folate deficiency. Polymyxin B: minimal systemic absorption, unlikely teratogenic. Overall, FDA category C/D for trimethoprim. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to polymyxin B, trimethoprim, or any component of the formulation."]
| Precautions | ["Hypersensitivity reactions, including anaphylaxis, have been reported.","Prolonged use may result in overgrowth of nonsusceptible organisms, including fungi.","Ophthalmic use only; not for injection or irrigation.","Patients should not wear contact lenses during treatment."] |
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| Fetal Monitoring | Monitor maternal folate status, CBC for megaloblastic anemia. Fetal ultrasound for neural tube defects and cardiac anomalies if exposed in first trimester. Monitor neonatal bilirubin and G6PD status. |
| Fertility Effects | No known adverse effects on human fertility. In animal studies, high-dose trimethoprim impaired spermatogenesis. Clinical significance unknown. |