What are the contraindications for Bactrim (trimethoprim/sulfamethoxazole)?

Contraindications for Trimethoprim/Sulfamethoxazole (Bactrim)

Trimethoprim/sulfamethoxazole (Bactrim) is absolutely contraindicated in patients with known hypersensitivity to trimethoprim or sulfonamides, history of drug-induced immune thrombocytopenia with trimethoprim or sulfonamides, documented megaloblastic anemia due to folate deficiency, pregnancy, nursing mothers, infants less than 2 months of age, and patients with marked hepatic damage or severe renal insufficiency when renal function cannot be monitored. 1

Absolute Contraindications

1. Hypersensitivity reactions:

   • Known hypersensitivity to trimethoprim or sulfonamides 2, 1
   • History of drug-induced immune thrombocytopenia with use of trimethoprim or sulfonamides 1

2. Hematologic conditions:

   • Documented megaloblastic anemia caused by folate deficiency 1

3. Special populations:

   • Pregnant patients (risk of kernicterus in the newborn) 1
   • Nursing mothers (drug is excreted in breast milk) 1
   • Pediatric patients less than 2 months of age 3, 1

4. Organ dysfunction:

   • Marked hepatic damage 1
   • Severe renal insufficiency when renal function status cannot be monitored 1

Relative Contraindications and Precautions

1. Renal impairment:

   • For creatinine clearance 15-30 mL/min: reduce to half the usual dosage 3
   • For creatinine clearance <15 mL/min: not recommended 3

2. Genetic disorders:

   • G6PD deficiency (risk of hemolytic anemia) 3

3. Drug interactions - use with caution with:

   • Methotrexate (potential for increased toxicity) 2
   • Oral anticoagulants (enhanced anticoagulant effect) 2
   • Antidiabetic agents (potential hypoglycemia) 2
   • Thiazide diuretics (increased risk of thrombocytopenia in elderly) 2
   • Anticonvulsants (potential decreased effectiveness) 2
   • Cyclosporine (increased nephrotoxicity) 2

Adverse Effects to Monitor

1. Severe cutaneous reactions:

   • Stevens-Johnson syndrome 2, 3
   • Toxic epidermal necrolysis 2, 3
   • Exfoliative dermatitis 2

2. Hematologic toxicity:

   • Agranulocytosis 2
   • Aplastic anemia 2, 3
   • Thrombocytopenia 2
   • Leukopenia 2
   • Neutropenia 2
   • Hemolytic anemia 2

3. Hepatic effects:

   • Fulminant hepatic necrosis 2, 3
   • Cholestatic jaundice 2
   • Elevation of serum transaminase and bilirubin 2

4. Renal effects:

   • Renal failure 2
   • Interstitial nephritis 2
   • Elevated BUN and creatinine 2
   • Crystalluria 2, 3

5. Neurologic effects:

   • Aseptic meningitis 2
   • Convulsions 2
   • Peripheral neuritis 2
   • Transient psychosis (rare but reported) 4

Clinical Decision Algorithm

1. Before prescribing TMP-SMX, screen for:

   • History of sulfonamide or trimethoprim allergies
   • Pregnancy or nursing status
   • Age (contraindicated in infants <2 months)
   • Renal and hepatic function
   • Current medications for potential interactions
   • History of blood dyscrasias or folate deficiency

2. During treatment, monitor for:

   • Complete blood count with differential at initiation and monthly during therapy 3
   • Skin reactions (discontinue immediately if severe rash develops)
   • Adequate hydration to prevent crystalluria 3
   • Renal function in at-risk patients

Important Clinical Pearls

• TMP-SMX is widely used but should be prescribed only for well-defined indications to prevent resistance development 5
• Serious toxicity is rare but can be life-threatening when it occurs 6
• Most common adverse reactions are gastrointestinal upset and skin eruptions 6, 5
• For mild to moderate skin rash, temporarily discontinue TMP-SMX and consider restarting when rash resolves 3
• For urticarial rash or Stevens-Johnson syndrome, permanently discontinue TMP-SMX 3
• Administer with food to decrease GI side effects 3

By carefully screening for contraindications and monitoring for adverse effects, clinicians can safely prescribe TMP-SMX when indicated while minimizing risks to patients.