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Trimethoprim and Polymyxin B

Generic name: polymyxin b/trimethoprim ophthalmic

Brand names: Polytrim

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, ophthalmic: Trimethoprim 1 mg and polymyxin B sulfate 10,000 units per 1 mL (10 mL)

Polytrim®: Trimethoprim 1 mg and polymyxin B sulfate 10,000 units per 1 mL (10 mL) [contains benzalkonium chloride]

Pharmacokinetics/Pharmacodynamics

Absorption

Trimethoprim and polymyxin B are systemically absorbed following ophthalmic installation. Peak concentrations were trimethoprim 0.03 mcg/mL and polymyxin B 1 unit/mL.

Use: Labeled Indications

Treatment of surface ocular bacterial conjunctivitis and blepharoconjunctivitis

Contraindications

Hypersensitivity to trimethoprim, polymyxin B, or any component of the formulation

Dosage and Administration

Dosing: Adult

Conjunctivitis, blepharoconjunctivitis: Ophthalmic: Instill 1 drop in affected eye(s) every 3 hours (maximum: 6 doses per day) for 7-10 days; has also been used 4 times daily for 5-7 days (Williams, 2013; The Wills Eye Manual, 2004)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Conjunctivitis, blepharoconjunctivitis: Infants ≥2 months, Children, and Adolescents: Ophthalmic: Instill 1 drop in eye(s) every 3 hours; maximum daily dose: 6 doses/day for 7 to 10 days; in children and adolescents, 4 times daily dosing for 5 to 7 days has also been used (Williams 2013)

Administration

Avoid contamination of the applicator tip.

Storage

Store at 15°C to 25°C (59°F to 77°F); protect from light.

Drug Interactions

Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy

Amantadine: Trimethoprim may enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Monitor therapy

Amodiaquine: Trimethoprim may enhance the neutropenic effect of Amodiaquine. Trimethoprim may increase the serum concentration of Amodiaquine. Avoid combination

Angiotensin II Receptor Blockers: Trimethoprim may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Trimethoprim may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy

AzaTHIOprine: Trimethoprim may enhance the myelosuppressive effect of AzaTHIOprine. Monitor therapy

Bacitracin (Systemic): Polymyxin B may enhance the nephrotoxic effect of Bacitracin (Systemic). Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Polymyxin B. Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Polymyxin B. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Colistimethate: Polymyxin B may enhance the neuromuscular-blocking effect of Colistimethate. Monitor therapy

CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapsone (Systemic): Trimethoprim may increase the serum concentration of Dapsone (Systemic). Dapsone (Systemic) may increase the serum concentration of Trimethoprim. Monitor therapy

Dapsone (Topical): Trimethoprim may enhance the adverse/toxic effect of Dapsone (Topical). More specifically, trimethoprim may increase the risk for hemolysis Monitor therapy

Digoxin: Trimethoprim may increase the serum concentration of Digoxin. Monitor therapy

Dofetilide: Trimethoprim may increase the serum concentration of Dofetilide. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification

Eplerenone: Trimethoprim may enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Fosphenytoin. Management: Consider alternatives to this combination when possible, to avoid potential decreased trimethoprim efficacy and increased phenytoin concentrations/effects. Monitor patients receiving this combination closely for both of these possible effects. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

LamiVUDine: Trimethoprim may increase the serum concentration of LamiVUDine. Monitor therapy

Leucovorin Calcium-Levoleucovorin: May diminish the therapeutic effect of Trimethoprim. Management: Avoid concurrent use of leucovorin or levoleucovorin with trimethoprim (plus sulfamethoxazole) for Pneumocystis jirovecii pneumonia. If trimethoprim is used for another indication, monitor closely for reduced efficacy. Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Monitor therapy

Mecamylamine: Polymyxin B may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Memantine: Trimethoprim may enhance the adverse/toxic effect of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Trimethoprim may increase the serum concentration of Memantine. Memantine may increase the serum concentration of Trimethoprim. Monitor therapy

Mercaptopurine: Trimethoprim may enhance the myelosuppressive effect of Mercaptopurine. Monitor therapy

MetFORMIN: Trimethoprim may increase the serum concentration of MetFORMIN. Monitor therapy

Methotrexate: Trimethoprim may enhance the adverse/toxic effect of Methotrexate. Management: Consider avoiding concomitant use of methotrexate and either sulfamethoxazole or trimethoprim. If used concomitantly, monitor for the development of signs and symptoms of methotrexate toxicity (e.g., bone marrow suppression). Consider therapy modification

Methoxyflurane: May enhance the nephrotoxic effect of Polymyxin B. Avoid combination

MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification

Neuromuscular-Blocking Agents: Polymyxin B may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Consider therapy modification

Phenytoin: Trimethoprim may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Trimethoprim. Management: Consider alternatives to this combination when possible, to avoid potential decreased trimethoprim efficacy and increased phenytoin concentrations/effects. Monitor patients receiving this combination closely for both of these possible effects. Consider therapy modification

PRALAtrexate: Trimethoprim may increase the serum concentration of PRALAtrexate. More specifically, trimethoprim may decrease excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum level and/or possible toxicity with concomitant use of trimethoprim. Monitor for decreased pralatrexate levels with discontinuation of trimethoprim. Monitor therapy

Procainamide: Trimethoprim may increase serum concentrations of the active metabolite(s) of Procainamide. Trimethoprim may increase the serum concentration of Procainamide. Consider therapy modification

Pyrimethamine: May enhance the adverse/toxic effect of Trimethoprim. Monitor therapy

Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Monitor therapy

RifAMPin: May decrease the serum concentration of Trimethoprim. Monitor therapy

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy

Sapropterin: Trimethoprim may decrease the serum concentration of Sapropterin. Specifically, trimethoprim may decrease tissue concentrations of tetrahydrobiopterin. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Spironolactone: Trimethoprim may enhance the hyperkalemic effect of Spironolactone. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Varenicline: Trimethoprim may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of trimethoprim, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Adverse Reactions

Frequency not defined:

Dermatologic: Circumocular rash

Ophthalmic: Burning sensation of eyes, eyelid edema, eye pruritus, eye redness (increased), lacrimation, stinging of eyes

Warnings/Precautions

See individual agents.

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed with trimethoprim in animal reproduction studies; animal reproduction studies have not been conducted with polymyxin B. See individual agents. If ophthalmic agents are needed during pregnancy, the minimum effective dose should be used in combination with punctal occlusion to decrease potential exposure to the fetus (Samples 1988).

Patient Education

What is this drug used for?

  • It is used to treat eye infections.

Frequently reported side effects of this drug

  • Burning
  • Stinging
  • Itching

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Vision changes
  • Eye pain
  • Severe eye irritation
  • Eyelid swelling
  • Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated January 31, 2020.