Usage
Sulfasalazine is primarily prescribed for:
- Inflammatory bowel disease (IBD): This includes ulcerative colitis and Crohn’s disease. It is used to treat active disease and maintain remission.
- Rheumatoid arthritis (RA): Sulfasalazine is employed when initial treatments like nonsteroidal anti-inflammatory drugs (NSAIDs) are ineffective.
- Juvenile idiopathic arthritis (JIA): Specifically, the polyarticular course of JIA.
Pharmacological classification: Sulfasalazine is classified as an aminosalicylate and a disease-modifying antirheumatic drug (DMARD). It exhibits anti-inflammatory and immunomodulatory properties.
Mechanism of action: While the exact mechanism isn’t fully understood, sulfasalazine is thought to work by reducing inflammation in the affected areas. It is metabolized into sulfapyridine and 5-aminosalicylic acid (mesalamine, 5-ASA) in the colon. 5-ASA is the primary anti-inflammatory component. The mechanism may involve inhibition of prostaglandin synthesis and other inflammatory mediators.
Alternate Names
- Sulphasalazine (International variation)
- Azulfidine (Brand name)
- Salazopyrin (Brand name)
How It Works
Pharmacodynamics: Sulfasalazine’s main effect is to decrease inflammation in the intestinal tract and joints. It does this by inhibiting the production of inflammatory mediators.
Pharmacokinetics:
- Absorption: Orally administered sulfasalazine is partially absorbed from the small intestine. Delayed-release formulations are designed to deliver the drug to the colon.
- Metabolism: The drug is metabolized by intestinal bacteria into sulfapyridine and 5-ASA.
- Elimination: Sulfasalazine and its metabolites are eliminated via both renal (kidney) and hepatic (liver) routes. A small amount of sulfasalazine and 5-ASA are excreted in breast milk.
Mode of action: 5-ASA acts locally on the colonic mucosa, suppressing inflammation. The mechanism involves inhibiting the production of inflammatory cytokines, prostaglandins, and leukotrienes. The role of sulfapyridine is less clear, and it may contribute to some of the adverse effects.
Receptor binding/Enzyme inhibition/Neurotransmitter modulation: Sulfasalazine does not directly bind to receptors or modulate neurotransmitters. Its anti-inflammatory action primarily stems from inhibiting the production of inflammatory mediators. It does inhibit folic acid absorption, requiring supplementation.
Elimination pathways: Sulfasalazine and its metabolites (sulfapyridine and 5-ASA) are excreted in both urine and feces.
Dosage
Standard Dosage
Adults:
- Ulcerative colitis:
- Initial: 3-4 g/day orally, divided into equal doses every 6-8 hours. In some cases, a lower initial dose of 1-2 g/day may be used to minimize gastrointestinal side effects.
- Maintenance: 2 g/day orally, divided into equal doses.
- Rheumatoid arthritis:
- Initial: 500-1000 mg/day orally, divided into two doses.
- Maintenance: 2000 mg/day orally, divided into two doses. Dosages up to 3000 mg/day can be used based on response and tolerance.
Children (6 years and older):
- Ulcerative colitis:
- Initial: 40-60 mg/kg/day orally, divided into 3-6 doses.
- Maintenance: 30 mg/kg/day orally, divided into 4 doses.
- Juvenile idiopathic arthritis:
- 30-50 mg/kg/day orally, divided into 2 doses, maximum 2 g/day. Start low and titrate upwards weekly until the maintenance dose is reached in one month to reduce gastrointestinal side effects.
Special Cases:
- Elderly Patients: Closely monitor for adverse events. No specific dose adjustments are routinely required but consider lower initial doses.
- Patients with Renal Impairment: Use with caution. Reduce dosage based on creatinine clearance.
- Patients with Hepatic Dysfunction: Use with caution. Monitor closely for adverse reactions. No specific dose adjustments are routinely required.
- Patients with Comorbid Conditions: Individualized dosing may be needed. For example, patients with diabetes may require closer glucose monitoring.
Clinical Use Cases
Sulfasalazine is not typically used in acute medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest.
Dosage Adjustments
Dose adjustments may be necessary for patients with renal or hepatic impairment, or those experiencing significant adverse effects. Genetic polymorphisms affecting drug metabolism may also warrant dose adjustment.
Side Effects
Common Side Effects:
- Nausea, vomiting, abdominal pain, diarrhea, anorexia
- Headache, dizziness, fatigue
- Rash, itching
Rare but Serious Side Effects:
- Agranulocytosis, leukopenia, thrombocytopenia
- Hepatitis, liver failure
- Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Lung inflammation (pneumonitis, interstitial lung disease)
Long-Term Effects:
- Infertility (reversible in males)
- Increased risk of infections
- Blood disorders
Adverse Drug Reactions (ADR):
- Severe allergic reactions (anaphylaxis)
- Blood dyscrasias
- Severe skin or liver toxicity
Contraindications
- Hypersensitivity to sulfasalazine, sulfapyridine, sulfonamides, salicylates, or any components of the formulation.
- Intestinal or urinary obstruction.
- Porphyria.
- Infants under 2 years of age.
Drug Interactions
- Folic acid: Sulfasalazine inhibits folic acid absorption.
- Digoxin: Reduced digoxin absorption.
- Methotrexate: Increased gastrointestinal side effects.
- Anticoagulants (e.g., warfarin): Enhanced anticoagulant effects.
- Antibiotics: Alterations in gut flora can affect sulfasalazine metabolism.
Pregnancy and Breastfeeding
- Pregnancy: Generally considered safe but folic acid supplementation is essential.
- Breastfeeding: Caution is advised, especially in premature infants or those with G6PD deficiency. Small amounts of sulfasalazine and metabolites are excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Reduces inflammation by inhibiting inflammatory mediators.
- Side Effects: Nausea, vomiting, headache, rash, rarely severe blood disorders or organ toxicity.
- Contraindications: Hypersensitivity, intestinal/urinary obstruction, porphyria.
- Drug Interactions: Folic acid, digoxin, methotrexate, anticoagulants.
- Pregnancy & Breastfeeding: Generally safe with folic acid supplementation during pregnancy. Caution during breastfeeding.
- Dosage: Varies depending on indication and age; start low and titrate up to minimize side effects.
- Monitoring Parameters: Complete blood counts, liver function tests, renal function tests.
Popular Combinations
- Methotrexate
- Hydroxychloroquine
- Other DMARDs
Precautions
- General Precautions: Monitor blood counts, liver and kidney function.
- Specific Populations: Close monitoring during pregnancy and breastfeeding. Use with caution in the elderly and those with renal/hepatic impairment.
- Lifestyle Considerations: No specific restrictions on alcohol or driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sulfasalazine?
A: Dosage varies depending on the condition and age. For adults with ulcerative colitis, the initial dose is 3-4 g/day divided every 6-8 hours. For rheumatoid arthritis, the initial adult dose is 500-1000 mg/day divided into two doses. Pediatric and special population dosing should be individualized.
Q2: How long does it take for Sulfasalazine to start working?
A: It may take several weeks or even months for the full therapeutic benefit of sulfasalazine to be realized.
Q3: What are the common side effects of Sulfasalazine?
A: Common side effects include nausea, vomiting, diarrhea, headache, and rash.
Q4: Can Sulfasalazine be taken during pregnancy?
A: Yes, it’s generally considered safe during pregnancy, but folic acid supplementation is crucial. Discuss with a healthcare professional.
Q5: Is Sulfasalazine safe during breastfeeding?
A: Caution is advised. It is excreted in breast milk and may affect infants, especially premature or G6PD deficient infants. Discuss with a healthcare professional.
Q6: What should I do if I miss a dose of Sulfasalazine?
A: Take the missed dose as soon as you remember, unless it’s close to the time of your next dose. Do not double the dose to catch up.
Q7: Does Sulfasalazine affect male fertility?
A: It can cause a reversible decrease in sperm count.
Q8: Are there any serious side effects of Sulfasalazine that I should be aware of?
A: Yes, rare but serious side effects include blood disorders (agranulocytosis, leukopenia), liver toxicity, severe skin reactions, and lung inflammation. Seek immediate medical attention if these occur.
Q9: Can Sulfasalazine be crushed or chewed?
A: No. Delayed-release tablets should be swallowed whole.
Q10: Does sulfasalazine interact with other medications?
A: Yes, it can interact with several medications like folic acid, digoxin, methotrexate and some antibiotics. Consult with a doctor about potential interactions.
