TRIMETHOPRIM SULFATE AND POLYMYXIN B SULFATE
Clinical safety rating: avoid
May increase levels of phenytoin and digoxin Can cause hyperkalemia and blood dyscrasias.
Trimethoprim inhibits bacterial dihydrofolate reductase, blocking tetrahydrofolate synthesis and thereby inhibiting thymidine synthesis. Polymyxin B disrupts bacterial cell membrane integrity by binding to lipopolysaccharides in Gram-negative bacteria.
| Metabolism | Trimethoprim is metabolized in the liver primarily via oxidation (O-demethylation and N-oxidation) and conjugation. Polymyxin B is not significantly metabolized; it is mainly excreted unchanged in urine. |
| Excretion | Trimethoprim: renal (80-90% unchanged, 10-20% metabolites); Polymyxin B: renal (60% unchanged, 40% nonrenal). |
| Half-life | Trimethoprim: 8-10 hours (normal renal function); Polymyxin B: 6 hours (prolonged in renal impairment). |
| Protein binding | Trimethoprim: 44% (weakly bound to albumin); Polymyxin B: 80% (bound to alpha-2-macroglobulin and albumin). |
| Volume of Distribution | Trimethoprim: 1.5-2.0 L/kg (high tissue penetration); Polymyxin B: 0.3-0.4 L/kg (limited to extracellular fluid). |
| Bioavailability | Topical/ophthalmic: minimal systemic absorption (<1%); oral/parenteral: not applicable for this combination. |
| Onset of Action | Topical: symptomatic relief within 24-48 hours; Ophthalmic: reduction of bacterial load within 12-24 hours. |
| Duration of Action | Topical: continued suppression with continued use; Ophthalmic: sustained effect with q.i.d. dosing. |
| Molecular Weight | Trimethoprim sulfate: 455.59 Da (as salt); Polymyxin B sulfate: 1301.56 Da (compound). For the combination, each component has its own molecular weight. |
One drop in each affected eye every 2 to 4 hours for 7 to 10 days.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No systemic absorption expected with ophthalmic use; no renal adjustment required. |
| Liver impairment | No systemic absorption expected with ophthalmic use; no hepatic adjustment required. |
| Pediatric use | Children: One drop in each affected eye every 2 to 4 hours for 7 to 10 days (same as adult dosing). |
| Geriatric use | Same as adult dosing; no specific dosage adjustment needed. |
| 1st trimester | Avoid use in first trimester due to potential folate antagonism and risk of neural tube defects. |
| 2nd trimester | Use only if clearly needed; consider alternative if possible due to possible hemolytic anemia in G6PD deficiency. |
| 3rd trimester | Avoid use near term due to risk of kernicterus and hemolytic anemia in neonates, especially with G6PD deficiency. |
Clinical note
May increase levels of phenytoin and digoxin Can cause hyperkalemia and blood dyscrasias.
| FDA category | Positive |
| Placental transfer | Trimethoprim crosses the placenta extensively achieving fetal serum concentrations similar to maternal levels. Polymyxin B crosses to a limited extent due to its molecular size and polarity. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Common Effects | Nausea |
| Serious Effects |
Hypersensitivity to trimethoprim or polymyxin BSevere renal impairment (CrCl < 15 mL/min) unless undergoing dialysisMegaloblastic anemia due to folate deficiency
| Precautions | Hypersensitivity reactions including anaphylaxis, Renal impairment: dose adjustment needed for trimethoprim, Electrolyte disturbances: hyperkalemia with high doses of trimethoprim, Neurological toxicity with polymyxin B: dizziness, ataxia, paresthesias, Superinfection with resistant organisms, Use caution in patients with folate deficiency or hematologic disorders |
| Food/Dietary | No known dietary restrictions or interactions. |
Loading safety data…
| Trimethoprim and polymyxin B are excreted into breast milk in small amounts. Trimethoprim may interfere with folate metabolism in the infant, especially if premature or ill. Administer with caution; monitor infant for rash, diarrhea, or jaundice. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Trimethoprim is a folate antagonist with known teratogenic potential in the first trimester, associated with neural tube defects, cardiovascular malformations, and oral clefts (odds ratio 2.0-3.4). Polymyxin B is not teratogenic in animal studies, but human data are limited. Risk in second and third trimesters includes potential for folate deficiency, megaloblastic anemia, and kernicterus due to bilirubin displacement from albumin by sulfonamide component; avoid near term. |
| Fetal Monitoring | Monitor complete blood count with differential and platelet count, renal function, and liver function tests monthly. Assess for signs of folate deficiency (megaloblastic anemia). In third trimester, monitor bilirubin levels in neonate. Ultrasound for fetal anomalies if used in first trimester. |
| Fertility Effects | Trimethoprim may impair folate metabolism, potentially affecting spermatogenesis and ovulation. No specific human data on fertility impairment. Animal studies show reduced implantation and fetal weight with high doses. |
| Clinical Pearls | This is a fixed-dose combination ophthalmic suspension used for bacterial conjunctivitis and blepharitis. Polymyxin B is a bactericidal against gram-negative bacteria; trimethoprim is a folate antagonist effective against gram-positive bacteria. Reserve for sensitive organisms. Monitor for hypersensitivity and corneal toxicity. Use with caution in sulfonamide allergy due to trimethoprim cross-reactivity. |
| Patient Advice | Shake the bottle well before each use. · Instill 1–2 drops in the affected eye(s) every 4 hours for 7–10 days. · Do not touch the dropper tip to any surface to avoid contamination. · Remove contact lenses before use and wait at least 15 minutes before reinserting. · Report any vision changes, severe eye pain, or worsening redness immediately. |