What are the potential side effects and clinical drug interactions of sulfasalazine?

Sulfasalazine Side Effects and Clinical Drug Interactions

Sulfasalazine has significant potential side effects including gastrointestinal symptoms, hematologic abnormalities, and various drug interactions that require careful monitoring and management. 1, 2

Common Side Effects

Gastrointestinal Effects (Occur in up to 33% of patients)

• Anorexia, nausea, vomiting, and gastric distress 2
• Abdominal pain and diarrhea 1
• Stomatitis 2

Hematologic Effects

• Reversible oligospermia 2
• Hemolytic anemia, Heinz body anemia 2
• Leukopenia, thrombocytopenia, agranulocytosis (rare but serious) 2, 3
• Megaloblastic anemia (related to folate deficiency) 2

Dermatologic Effects

• Skin rash, pruritus, urticaria 2
• More severe reactions: erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis 2

Neurological Effects

• Headache (common) 2, 3
• Less common: dizziness, insomnia, depression, peripheral neuropathy 2

Other Effects

• Fever 2
• Cyanosis 2
• Arthralgia 3
• Abnormal liver function tests 3

Serious Adverse Reactions (Rare)

• Hepatitis and hepatic necrosis (potentially fatal) 2
• Pancreatitis 2
• Interstitial lung disease, pneumonitis 2
• Lupus-like syndrome 2
• Pericarditis 2
• Renal reactions: toxic nephrosis, nephritis, nephrotic syndrome 2

Drug Interactions

Reduced Absorption

• Reduces absorption of folic acid (supplementation recommended) 1
• Reduces absorption of digoxin 1
• Antacids containing aluminum and magnesium may affect absorption 1
• Calcium and iron supplements may reduce absorption 1

Other Interactions

• Cholestyramine (may reduce sulfasalazine absorption) 1
• High-dose salicylates 1
• Phenytoin 1
• Xanthine bronchodilators 1
• Probenecid 1
• Antivirals: acyclovir, ganciclovir, valganciclovir 1

Monitoring Requirements

Baseline Testing

• Complete blood count (CBC) with differential 1
• Liver function tests 1
• Chemistry panel 1
• Pregnancy test if indicated 1

Ongoing Monitoring

• CBC and platelet counts:
  • Weekly for first month
  • Every 2 weeks for next 2 months
  • Monthly thereafter 1
• Monthly chemistry panel and liver function tests 1
• Periodic urinalysis and renal function tests 1

Special Populations

Pregnancy and Breastfeeding

• FDA pregnancy category B (relatively safe) 1
• Sulfasalazine is considered safe during pregnancy and lactation 4
• However, sulfonamides in breast milk can compete with bilirubin for binding sites on plasma proteins in newborns, potentially causing kernicterus 1

Male Fertility

• May cause reversible male infertility/oligospermia 2, 4

Management of Side Effects

Dose-Related Side Effects

• Many common side effects (GI symptoms, headache) can be managed by dosage adjustment 4
• Slow introduction of the medication is recommended (starting with lower doses) 3
• Enteric-coated tablets are preferred to reduce upper GI side effects 3

Allergic Reactions

• For allergic reactions (rash, fever, arthralgia), desensitization may be possible 4
• Idiosyncratic reactions are absolute contraindications to further use 4

Clinical Pearls

• Side effects are most common in the first 3 months of treatment 3
• 20-30% of patients discontinue treatment due to adverse reactions 3
• Side effects leading to withdrawal after 1 year of therapy are unusual 3
• Risk of side effects increases with doses above 4g daily or serum sulfapyridine levels above 50 mcg/mL 2
• Folate supplementation is recommended to prevent megaloblastic anemia 1
• Enteric-coated formulations may help reduce GI side effects 3
• Regular laboratory monitoring is essential to detect potentially serious hematologic and hepatic adverse effects early 5

By understanding these side effects and interactions, clinicians can appropriately monitor patients and intervene early to prevent serious complications while maximizing therapeutic benefits of sulfasalazine.