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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
May increase levels of phenytoin and digoxin Can cause hyperkalemia and blood dyscrasias.
| FDA category | Positive |
| Breastfeeding | Trimethoprim and polymyxin B are excreted into breast milk. M/P ratio for trimethoprim is approximately 0.6-1.2. Polymyxin B has poor oral bioavailability, so systemic exposure to infant is minimal. However, sulfonamides can cause kernicterus in neonates with G6PD deficiency or hyperbilirubinemia. Avoid in breastfeeding if infant is premature, jaundiced, or G6PD deficient. |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | Nausea |
| Serious Effects |
["Known hypersensitivity to either component","Severe renal impairment (CrCl <15 mL/min) without dose adjustment","Breastfeeding (polymyxin B may be excreted, potential for infant toxicity)"]
| 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"] |
Loading safety data…
| 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. |