Sulfasalazine is a synthetic salicylic acid derivative with affinity for connective tissues containing elastin and formulated as a prodrug, antiinflammatory Sulfasalazine acts locally in the intestine through its active metabolites, sulfamide 5-aminosalicylic acid and salicylic acid, by a mechanism that is not clear. It appears inhibit cyclooxygenase and prostaglandin production and is used in the management of inflammatory bowel diseases.
Sulfasalazine a drug that is used in the management of rheumatoid arthritis, ulcerative colitis, and Crohn’s disease, inflammatory bowel diseases. It is often considered as a first line treatment in rheumatoid arthritis. It is taken by mouth. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid released in the colon
Mechanism of Action of Sulfasalazine
The mode of action of Sulfasalazine or its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), is still under investigation, but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and in vitro models, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver, and intestinal walls, as demonstrated in autoradiographic studies in animals. In ulcerative colitis, clinical studies utilizing rectal administration of Sulfasalazine, SP, and 5-ASA have indicated that the major therapeutic action may reside in the 5-ASA moiety. The relative contribution of the parent drug and the major metabolites in rheumatoid arthritis is unknown.
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The purpose of the present study was to determine whether sulfasalazine therapy affected NF-kappaB activation and the expression of pro-inflammatory cytokines in patients with ulcerative colitis. … A total of 38 patients with moderate ulcerative colitis were investigated. Twenty-one patients received sulfasalazine. Seventeen patients did not receive any medication. Biopsy specimens were obtained from the inflamed mucosa and analyzed for NF-kappaB DNA binding activity, NF-kappaBp65/IkappaBalpha protein expression and the levels of pro-inflammatory cytokine mRNA using electrophoretic mobility shift assay, western blot analysis, immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively. Increased activation of NF-kappaB and high levels of the expression of interleukin (IL)-1beta mRNA and IL-8 mRNA were detected in biopsy specimens from patients with ulcerative colitis. Therapeutic administration of sulfasalazine effectively downregulated the activation of NF-kappaB and the expression of IL-1beta mRNA and IL-8 mRNA while IkappaBalpha levels were stable. /The authors concluded that/ the therapeutic benefits for ulcerative colitis of sulfasalazine might at least in part be attributed to its ability to inhibit NF-kappaB activation, resulting in the downregulation of pro-inflammatory cytokine mRNA expression.
Indications of Sulfasalazine
- For the treatment of Crohn’s disease and rheumatoid arthritis as a second-line agent.
- Rheumatoid Arthritis
- Ankylosing Spondylitis
- Multiple joint pain
- Morning stiffness
- Inflammatory Bowel Disease
- Crohn’s Disease
- Juvenile Rheumatoid Arthritis
- Lymphocytic Colitis
- Psoriatic Arthritis
- Ulcerative Colitis
- Polyarticular juvenile rheumatoid arthritis, chronic or unspecified
- Proctitis
- Mild Ulcerative Colitis
- Alopecia
Contra-Indications of Sulfasalazine
Patients with intestinal or urinary obstruction, Patients with porphyria as sulfonamides have been reported to precipitate an acute attack, Patients hypersensitive to sulfasalazine, its metabolites, sulfonamides, or salicylates.
- Severe infection
- Glucose-6-Phosphate Dehydrogenase Deficiency
- Porphyria
- Low Blood Counts due to Bone Marrow Failure
- Decreased Neutrophils a Type of White Blood Cell
- Asthma
- Stomach or Intestine Blockage
- Liver Problems
- Kidney disease with reduction in kidney function
- Urinary Tract Blockage
- Anemia from Pyruvate Kinase and Deficiencies
- Slow Acetylator
Allergies
- Salicylates
- NSAIDs (Non-Steroidal Anti-Inflammatory Drug)
- Sulfa (Sulfonamide Antibiotics)
- Sulfasalazine
Dosage of Sulfasalazine
Strength: 500 mg, 1000 mg
Rheumatoid Arthritis
- Delayed-release tablets: 1000 mg orally twice a day
Suggested dosing regimen
- Week 1: 500 mg orally once a day in the evening
- Week 2: 500 mg orally twice a day (morning and evening)
- Week 3: 500 mg orally in the morning and 1000 mg in the evening
- Week 4: 1000 mg orally twice a day (morning and evening)
- For maintenance therapy, the dose is 2,000 mg per day taken in 2 evenly divided and evenly spaced doses.
Ulcerative Colitis
- 3 to 4 g/day orally in evenly divided doses
Crohn’s Disease
- 3 to 6 g/day orally in divided doses
juvenile rheumatoid arthritis
- The maintenance dose is 30–50 mg/kg of body weight per day taken in two evenly divided and evenly spaced doses.
Uveitis
- Initial dose: 500 mg/day, then increased by 500 mg/week
- Maintenance dose: 1 g twice a day for 1 year; in cases of a new flare, the dose was increased by 500 mg/week up to 3 g/day
Usual Pediatric Dose
Ulcerative Colitis
6 years or older
- Initial therapy: 40 to 60 mg/kg/day orally divided into 3 to 6 doses
- Maintenance therapy: 30 mg/kg/day orally divided into 4 doses
Juvenile Rheumatoid Arthritis
- 6 years or older: 30 to 50 mg/kg/day orally in 2 equally divided doses
- Maximum dose: 2 g/day (normally)
Side Effects of Sulfasalazine
The most common
- stomach pain, especially if it comes along with fever and diarrhea or constipation
- yellowing of the skin or eyes
- loss of appetite
- Constipation
- sleepiness or unusual drowsiness
- clumsiness or unsteadiness
- dizziness
- drowsiness
- dry mouth
- false sense of well-being
- increased watering of mouth
- lightheadedness
- constipation;
- vision changes;
- breast swelling (in men or women); or
- decreased sex drive, impotence, or difficulty having an orgasm.
- blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- restless muscle movements in your eyes, tongue, jaw, or neck;
Common
- Drowsiness and lightheadedness the day after taking the medicine.
- Confusion.
- Numbed emotions.
- Visual disturbances such as blurred vision or double vision.
- Shaky movements and unsteady walk (ataxia).
- Loss of memory (amnesia).
- Muscle weakness.
- Dizziness.
- A headache.
- Skin rashes.
- Disturbances of the gut such as diarrhea, constipation, nausea, vomiting or abdominal pain.
- Difficulty in passing urine (urinary retention).
- Changes in sex drive.
- Low blood pressure (hypotension).
- Blood disorders.
- Jaundice.
- Unexpected aggression, restlessness or irritability (tell your doctor if you experience this).
- Nightmares or hallucinations (tell your doctor if you experience this).
Rare
- agitation
- anxiety
- behavioural changes, including aggressiveness, angry outbursts, bizarre behavior, or decreased inhibitions
- confusion
- increased trouble sleeping
- memory problems
- muscle spasms
- shortness of breath
Drug Interactions of Sulfasalazine
Sulfasalazine may interact with following drugs, supplyments, & may change the efficacy of drugs
- abatacept
- anakinra
- anti-tumour necrosis factor agents (e.g., adalimumab, etanercept, infliximab, )
- azathioprine
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- beta-blockers (e.g., carvedilol, metoprolol, propranolol)
- carbamazepine
- clonidine
- clozapine
- corticosteroids (e.g.dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- diltiazem
- imatinib
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- methotrexate
- methyldopa
- mycophenolate
- phenobarbital
- phenytoin
- rituximab
- tacrolimus
- verapamil
Pregnancy & Lactation of Sulfasalazine
FDA Pregnancy Category B
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
This medication passes into breast milk. If you are a breastfeeding mother and are taking sulfasalazine, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. This medication is not recommended for children with juvenile rheumatoid arthritis.
References
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Sulfasalazine (Oral route)
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