Trimethoprim (Alprim) is an antibiotic that acts by inhibiting bacterial folate activation to tetrahydrofolate inhibiting bacterial protein and nucleic acid synthesis. It is used in the treatment of acute urinary tract infection, otitis media, and pneumocystis pneumonia infection.

Trimethoprim Uses:

• Treatment of uncomplicated acute Cystitis (tablets, oral solution):

  • It is indicated for the treatment of uncomplicated urinary tract infections caused by susceptible strains of the following organisms:
    • Escherichia coli,
    • Proteus mirabilis,
    • Klebsiella pneumoniae,
    • Enterobacter species and
    • coagulase-negative Staphylococcus species, including S. saprophyticus.

• Acute Otitis media (oral solution):

  • It is used to treat acute otitis media in children caused by susceptible strains of Streptococcus pneumoniae and Haemophilus influenzae.

• Off Label Use of Trimethoprim in Adults:

  • Acne vulgaris;
  • Treatment of mild to moderately severe pneumocystis pneumonia infection;
  • Prophylaxis of urinary tract infection.

Trimethoprim (Alprim) Dose in Adults

Trimethoprim (Alprim) Dose in the treatment of treatment of acute uncomplicated Cystitis:

• 100 mg orally twice daily for 3 days.

• Manufacturer's labeling:

  • 200 mg once a day (The dosing mentioned here may not reflect the current practice guidelines).

Trimethoprim (Alprim) Dose in the treatment of Acne vulgaris as an alternative therapy (off-label):

• 100 mg orally thrice daily or 300 mg two times a day.
• Treatment should be given for the shortest possible time to minimize bacterial resistance. Patients must be evaluated every three to four months.

Trimethoprim (Alprim) Dose as an alternative agent in the treatment of mild to moderate Pneumocystis pneumonia (off-label use):

• Oral: 15 mg/kg/day in three divided doses in combination with dapsone for 21 days.

Trimethoprim (Alprim) Dose for the prophylaxis of uncomplicated Urinary tract infection (off-label):

• 100 mg orally once a day.

Trimethoprim (Alprim) Dose in Childrens

Trimethoprim (Alprim) Dose in the treatment of acute Otitis media:

• Infants ≥6 months, Children, and Adolescents:

  • 10 mg/kg/day orally in two divided doses administered every 12 hours for ten days.
  • The maximum daily dose is 400 mg/day.

Trimethoprim (Alprim) Dose in the treatment of uncomplicated urinary tract infection:

• Infants ≥2 months, Children, and Adolescents:

  • 4 to 6 mg/kg/day orally in divided doses administered twice daily;
  • Note: The combination product sulfamethoxazole and trimethoprim is preferred.

Trimethoprim (Alprim) Dose in the treatment of Pneumocystis jirovecii pneumonia (PCP):

• Children and Adolescents:

  • 15 mg/kg/day orally in three divided doses in combination with dapsone for 21 days.
  • Data in children is limited. The combination product, sulfamethoxazole and trimethoprim is preferred.

Pregnancy Risk Factor C

• It may cross the placental boundary. It can cause adverse fetal outcomes due to its effect on folate metabolism.
• Also, read the sulfamethoxazole/trimethoprim monograph for details

Trimethoprim use during breastfeeding:

• Breast milk contains the drug, and its concentration is identical in maternal blood and breastmilk.
• Breastmilk can contain antibiotics which may cause side effects, such as diarrhea and oral thrush.
• It can also interfere with folate metabolism and is not recommended for breastfeeding.
• Products that do not contain the combination (trimethoprim) are compatible with breastfeeding.
• Also, read septran.

Dose in Kidney Disease:

• Manufacturer's labeling:

  • CrCl >30 mL/minute: Use with caution, however, no dosage adjustment is necessary.
  • CrCl 15 to 30 mL/minute: Administer half of the recommended dose.
  • CrCl <15 mL/minute: Avoid in advanced renal disease.

• Alternate recommendations:

  • Aronoff 2007: Note: Dose adjustments mentioned here are based on the usual daily dose of 100 mg twice a day.
    • CrCl >30 mL/minute: No dosage adjustment necessary.
    • CrCl 10 to 30 mL/minute: 100 mg administered every 18 hours.
  • CrCl <10 mL/minute: 100 mg once a day.
  • Intermittent Hemodialysis: It is 20% to 59% dialyzable. Administration of the dose after dialysis is recommended.
  • Peritoneal dialysis: 100 mg once a day.

• HHS (OI adult 2019):

  • Treatment of Pneumocystis pneumonia:
    • Note: Dosage adjustments mentioned here are based on the usual maintenance dose of 5 mg/kg administered every 8 hours. Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.
    • CrCl >30 mL/minute: No dosage adjustment necessary.
    • CrCl 10 to 30 mL/minute: 5 mg/kg twice daily.
    • CrCl <10 mL/minute: 5 mg/kg once daily.
    • Intermittent Hemodialysis:
      • It is moderately dialyzable, about 20% to 59%.
      • 5 mg/kg once daily. The dose is administered after hemodialysis on the day of dialysis.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling. It should be used with caution in patients with liver disease. 

Side effects of Trimethoprim (Alprim):

• Dermatologic:

  • Maculopapular Rash
  • Phototoxicity
  • Pruritus

• Endocrine & Metabolic:

  • Hyperkalemia
  • Hyponatremia

• Gastrointestinal:

  • Epigastric Distress
  • Glossitis
  • Nausea
  • Vomiting

• Hematologic & Oncologic:

  • Leukopenia
  • Megaloblastic Anemia
  • Methemoglobinemia
  • Neutropenia
  • Thrombocytopenia

• Hepatic:

  • Increased Liver Enzymes

• Hypersensitivity:

  • Anaphylaxis
  • Hypersensitivity Reaction

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine

• Miscellaneous:

  • Fever

Contraindications to Trimethoprim (Alprim):

• Allergy reactions to trimethoprim and any component of the formulation
• Megaloblastic anemia due to folate deficiency

Warnings and precautions

• Hematologic effects

  • Long-term treatment or high doses of medication may lead to cytopenias, bone marrow suppression, and even death.
  • Long-term therapy patients should be closely monitored for signs and symptoms of bone tumor suppresion.

• Hyperkalemia:

  • Treatment may result in hyperkalemia. Hyperkalemia is a risk for patients who are:
    • High doses (above 20 mg/kg/day)
    • Patients with severe renal impairment
    • Ageing is a good thing
    • Hypoaldosteronism is a form of and
    • Patients taking concomitant medication that can cause or exacerbate hyperkalemia.

• Hypersensitivity

  • Rarely, severe allergic reactions can occur.

• Superinfection

  • Long-term use can lead to superinfections, including fungal or bacterial infections.
  • Patients receiving long-term treatment may experience pseudomembranous colitis and C. difficile-associated diarrhea. 
  • This may occur up to two months after the last treatment.

• Hepatic impairment

  • Patients with hepatic impairment need to be cautious.

• Renal impairment

  • It should be used with caution by patients with impaired renal function.

Trimethoprim: Drug Interaction

Monitoring parameters:

Monitor CBC with differential counts, platelet count, liver function tests, bilirubin, serum potassium, serum creatinine, and BUN periodically in patients on long-term treatment.

How to administer Trimethoprim (Alprim)?

• It is administered without regard to meals.
• It may be administered with food or milk to reduce the gastrointestinal side effects. 

Mechanism of action of Trimethoprim (Alprim):

• It inhibits bacterial nucleic acids synthesis and proteins by reversibly inhibiting dihydrofolate reductase. 
• This causes the inhibition of folic acids conversion to tetrahydrofolate, which is active folate. It is necessary for the production of nucleic acids and proteins in bacteria.

Absorption:

• When taken orally, it is easily absorbed.

Distribution:

• It is found in many body tissues and fluids, including the middle ear, CSF, Bile and prostate.

Protein binding:

• About 44%

Metabolism:

• It is partially metabolized in the liver (10% to 20%) via demethylation, oxidation, and hydroxylation

Bioavailability:

• Similar for tablets and solution

Half-life elimination:

• Half-life elimination is prolonged with renal impairment
• Newborns: 19 hours (range: 11 to 27 hours)
• Infants 2 months to 1 year: 4.6 hours (range: 3 to 6 hours)
• Children:
  • 1 to 3 years: 3.7 hours
  • 8 to 10 years: 5.4 hours
• Adults with normal renal function: 8 to 10 hours

Time to peak serum concentration:

• 1 to 4 hours

Excretion:

• It is primarily excreted in urine (50% to 60%; 80% as unchanged drug);
• feces

International Brand Names of Trimethoprim:

• Primsol
• Trimpex
• Abaprim
• Alprim
• Antrin
• Catin
• Epirim
• Giprim
• Idotrim
• Infectotrimet
• Monotrim
• Motrim
• Primosept
• Sinersul
• Solotrim
• Sulotrim
• Tediprima
• Tobyprim
• Trimcort
• Trimesan
• Trimetin
• Trimetop
• Trimetoprim
• Trimol-A
• Trimopan
• Trimoptin
• Triprim
• Urotrim
• Utisept
• Wellcoprim

Trimethoprim Brand Names in Pakistan: