What are the side effects of Bactrim (sulfamethoxazole and trimethoprim)?

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Bactrim's Side Effects

Bactrim (sulfamethoxazole-trimethoprim) can cause numerous serious adverse effects including potentially fatal skin reactions, blood disorders, and liver damage, requiring careful monitoring during treatment. 1, 2

Common Side Effects

Bactrim commonly causes several side effects that patients should be aware of:

Gastrointestinal Effects

  • Nausea and vomiting
  • Diarrhea
  • Abdominal pain
  • Anorexia (loss of appetite)
  • Stomatitis and glossitis (inflammation of mouth and tongue) 1, 2

Dermatologic Effects

  • Rash (most common allergic reaction)
  • Pruritus (itching)
  • Photosensitivity (increased sensitivity to sunlight)
  • Urticaria (hives) 3, 1

General Effects

  • Headache
  • Fatigue and weakness
  • Insomnia 3

Serious Side Effects

Severe Cutaneous Adverse Reactions (SCARs)

  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
  • Acute febrile neutrophilic dermatosis (AFND)
  • Acute generalized erythematous pustulosis (AGEP) 2

Hematologic Effects

  • Agranulocytosis
  • Aplastic anemia
  • Thrombocytopenia
  • Leukopenia and neutropenia
  • Hemolytic anemia
  • Megaloblastic anemia (due to folate deficiency) 3, 2

Hepatic Effects

  • Hepatitis
  • Cholestatic jaundice
  • Hepatic necrosis
  • Elevation of serum transaminases and bilirubin 3, 2

Renal Effects

  • Renal failure
  • Interstitial nephritis
  • Elevated BUN and serum creatinine
  • Crystalluria
  • Nephrotoxicity (especially when used with cyclosporine) 3

Metabolic Effects

  • Hyperkalemia (especially in AIDS patients and elderly)
  • Hyponatremia
  • Metabolic acidosis 1, 2

Neurologic Effects

  • Aseptic meningitis
  • Convulsions
  • Peripheral neuritis
  • Ataxia
  • Vertigo
  • Tinnitus 3, 4

Cardiovascular Effects

  • QT prolongation
  • Ventricular tachycardia
  • Torsades de pointes
  • Circulatory shock 2

Respiratory Effects

  • Cough
  • Shortness of breath
  • Pulmonary infiltrates
  • Acute eosinophilic pneumonia
  • Acute and delayed lung injury
  • Interstitial lung disease
  • Acute respiratory failure 2

High-Risk Populations

Certain patient populations require special attention when prescribed Bactrim:

  1. Elderly patients: More susceptible to adverse effects, especially when taking thiazide diuretics 1

  2. Patients with renal impairment: Require dose adjustment when creatinine clearance is <30 mL/min 5

  3. Patients with hepatic dysfunction: Higher risk of toxicity 1

  4. Patients with possible folate deficiency: Including elderly, chronic alcoholics, patients on anticonvulsants, and those with malnutrition 1

  5. Patients with G6PD deficiency: Risk of hemolysis 1

  6. AIDS patients: Higher incidence of side effects, particularly rash, fever, leukopenia, and elevated transaminases 1

  7. Pregnant women: Pregnancy category C; sulfonamides may cause kernicterus in neonates 3

  8. Nursing mothers: Both components are distributed into breast milk 3

Drug Interactions

Bactrim has numerous significant drug interactions:

  • Anticoagulants: Potentiates warfarin activity 3
  • Diuretics: Increased risk of thrombocytopenia with thiazides 1
  • Methotrexate: Increased methotrexate levels and antifolate effects 3
  • Phenytoin: Reduced metabolism, monitor levels 3
  • Cyclosporine: Increased risk of nephrotoxicity 3
  • Digoxin: May increase serum levels in elderly 1
  • Oral hypoglycemic agents: Risk of hypoglycemia 3
  • Dapsone: Possible increased risk of methemoglobinemia 3
  • Tricyclic antidepressants: Potential interaction 3

Monitoring Recommendations

To minimize risks associated with Bactrim therapy:

  1. Complete blood counts: Perform frequently; discontinue if significant reduction in any blood element 1

  2. Urinalysis and renal function tests: Particularly important for patients with impaired renal function 1

  3. Liver function tests: Monitor for hepatotoxicity 2

  4. Serum potassium: Close monitoring in patients with underlying disorders of potassium metabolism, renal insufficiency, or taking drugs known to induce hyperkalemia 1

  5. Adequate fluid intake: Ensure sufficient hydration to prevent crystalluria 1

Clinical Pearls and Pitfalls

  1. Early recognition of hypersensitivity: Discontinue immediately if rash or any sign of adverse reaction develops, especially in AIDS patients 1

  2. Folate supplementation: Consider in high-risk patients to prevent hematologic complications 1

  3. Avoid in sulfa-allergic patients: Cross-reactivity is common 2

  4. Complete full course: Skipping doses may decrease effectiveness and increase bacterial resistance 1

  5. Avoid in late pregnancy: Risk of kernicterus in neonates 3

  6. Avoid with trimethoprim: When used for acne treatment, use as monotherapy should be avoided 3

  7. Be aware of rare but serious reactions: Some adverse effects like Stevens-Johnson syndrome can be fatal 6, 7

References

3
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

5
Research

Trimethoprim-sulfamethoxazole.

Mayo Clinic proceedings, 1991

7
Research

Trimethoprim-sulfamethoxazole-associated hepatotoxicity - part of a hypersensitivity syndrome.

The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique, 2003

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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