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. |
| Molecular Weight | Trimethoprim: 290.32 Da; Sulfacetamide: 214.24 Da |
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 | Avoid use due to potential teratogenicity from trimethoprim, a folate antagonist, unless clearly needed. Limited human data. |
| 2nd trimester | Use only if potential benefit justifies risk to fetus. Trimethoprim may interfere with folic acid metabolism; avoid in the second trimester if possible. |
| 3rd trimester | Avoid use near term due to theoretical risk of kernicterus from sulfonamide component (sulfacetamide) displacing bilirubin, and possible neonatal hemolysis. |
Clinical note
Comprehensive clinical and safety monograph for POLYTRIM (POLYTRIM).
| Placental transfer | Both trimethoprim and sulfacetamide cross the placenta. Trimethoprim reaches fetal concentrations approximately 50-100% of maternal serum levels. Sulfacetamide transfer is moderate. |
| Breastfeeding | Trimethoprim and sulfacetamide are excreted into breast milk in low amounts. The American Academy of Pediatrics considers trimethoprim compatible with breastfeeding. Monitor infant for jaundice, hemolysis, and rash. Use caution in infants with G6PD deficiency. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to any component (trimethoprim, sulfacetamide, or sulfonamides)Megaloblastic anemia due to folate deficiencySevere hepatic or renal impairmentInfants younger than 2 months (risk of kernicterus from sulfonamide)
| 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. |
| Food/Dietary | No significant food interactions known. Avoid alcohol as it may cause transient flushing due to polymyxin B's histamine-releasing effect in rare cases. |
Loading safety data…
| Lactation Rating | L2 (Safe) |
| 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. |
| 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. |
| Clinical Pearls | Polymyxin B/Trimethoprim ophthalmic solution is a fixed-dose combination indicated for bacterial conjunctivitis and blepharitis. Due to polymyxin B's poor systemic absorption, it is safe in pregnancy and renal impairment. Trimethoprim resistance is emerging, so culture and sensitivity should be considered for refractory cases. The solution is contraindicated in patients with known hypersensitivity to any component. Administer 1 drop every 3 hours for 7-10 days. Do not use for more than 10 days unless instructed. Contact lens wear should be avoided during treatment. |
| Patient Advice | Shake the bottle well before each use. · Do not touch the dropper tip to your eye or any surface to avoid contamination. · Wait at least 5 minutes between applying different eye medications. · Remove contact lenses before applying and wait 15 minutes before reinserting. · Complete the full course even if symptoms improve. · Report worsening symptoms, eye pain, or vision changes to your doctor. · Do not share your medication with others. |