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Peds Calc

Safety Information

Sulfamethoxazole - Trimethoprim Contraindications & InteractionsWhen Not to Use & Important Drug Interactions

Understanding contraindications for sulfamethoxazole-trimethoprim is critical due to the relatively common occurrence of sulfa allergies and important drug interactions. Careful screening helps prevent serious adverse reactions and treatment failures.

Clinical Utility: /10
4 Clinical Sources
Back to Sulfamethoxazole - Trimethoprim Overview

Key contraindications include documented sulfa allergies, age under 2 months, severe renal impairment, folate deficiency anemia, and significant drug interactions with methotrexate and potassium-raising medications. The dual mechanism requires consideration of contraindications for both components.

Contraindications

Absolute Contraindications (Never Use)

Unspecified condition

History of hypersensitivity reactions to any sulfonamide medication

Unspecified condition

Risk of kernicterus from bilirubin displacement

Unspecified condition

Trimethoprim further inhibits folate metabolism

Relative Contraindications (Use With Caution)

Severe Liver or Kidney Dysfunction

Use is contraindicated in children with marked hepatic damage or significant renal impairment unless closely monitored and dose-adjusted. Impaired clearance can lead to drug accumulation and increased toxicity. Monitoring of renal function and electrolytes is important, especially during prolonged therapy.

Megaloblastic Anemia Due to Folate Deficiency

SMX-TMP interferes with folic acid metabolism, so it should not be used in children with documented folate deficiency–related anemias unless under close hematologic supervision. In these patients, alternative antibiotics may be safer.

Cautions with Drug Interactions

Avoid concurrent use with drugs like methotrexate or phenytoin without specialist guidance, as SMX-TMP can displace these agents from protein-binding sites and interfere with metabolism, increasing toxicity. Also use caution in children taking ACE inhibitors or potassium-sparing diuretics, as the combination may increase the risk of hyperkalemia.

Pregnancy & Lactation

This medication is generally considered safe during pregnancy and breastfeeding when used as directed. However, if you're pregnant or breastfeeding and need to give this medication to your child, it's always a good idea to discuss this with your healthcare provider to ensure it's the best choice for your specific situation.

Drug Interactions

major interaction

Specific drugs: See description

Effect: Severe bone marrow suppression, mucositis

How it happens: Displacement from protein binding and decreased renal clearance

Management: Avoid combination or monitor with extreme caution

major interaction

Specific drugs: See description

Effect: Increased bleeding risk, elevated INR

How it happens: Inhibition of warfarin metabolism, displacement from proteins

Management: Monitor INR closely, adjust warfarin dose

moderate interaction

Specific drugs: See description

Effect: Risk of dangerous hyperkalemia

How it happens: Both drugs can increase potassium levels

Management: Monitor potassium levels, especially with renal impairment

moderate interaction

Specific drugs: See description

Effect: Phenytoin toxicity: ataxia, nystagmus, confusion

How it happens: Inhibition of phenytoin metabolism

Management: Monitor phenytoin levels, adjust dose if needed

moderate interaction

Specific drugs: See description

Effect: Digoxin toxicity: nausea, arrhythmias

How it happens: Reduced gut bacteria that metabolize digoxin

Management: Monitor digoxin levels in susceptible patients

Safety Screening Tools

Pre-Administration Screening Questions

1

Screening question

If yes: Consult healthcare provider

2

Screening question

If yes: Consult healthcare provider

3

Screening question

If yes: Consult healthcare provider

4

Screening question

If yes: Consult healthcare provider

5

Screening question

If yes: Consult healthcare provider

6

Screening question

If yes: Consult healthcare provider

Monitoring Requirements

Complete blood count

Frequency

Baseline and weekly for prolonged therapy

Action Thresholds:

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Renal function

Frequency

Baseline and as indicated

Action Thresholds:

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Potassium levels

Frequency

If risk factors present

Action Thresholds:

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Clinical monitoring

Frequency

Ongoing during therapy

Clinical Pearls

True sulfa allergy prevalence is lower than reported

Evidence: Not specifiedSource: Unknown

Hydration is therapeutic, not just supportive

Evidence: Not specifiedSource: Unknown

Cross-reactivity with non-antibiotic sulfonamides is rare

Evidence: Not specifiedSource: Unknown

Trimethoprim component can cause isolated hyperkalemia

Evidence: Not specifiedSource: Unknown

Clinical References

Sulfamethoxazole-Trimethoprim Drug Interactions and ContraindicationsClinical Pharmacology Database (2023)drug referencePediatric data
Sulfonamide Allergy Cross-ReactivityJournal of Allergy and Clinical Immunology (2022)systematic review
Safety of Antibiotics in Pediatric Patients with Reported AllergiesPediatric Infectious Disease Journal (2023)clinical studyPediatric data
Drug-Drug Interactions in Pediatric Antimicrobial TherapyPediatric Pharmacology Reviews (2023)expert reviewPediatric data