Brand Name : SALAZO
Generic Name : Sulfasalazine
Preparation : 500 mg Enteric Coated Tablet
Pharmacological Categories : DMARD (Disease Modifying Antirheumatoid Drug) / Anti-inflammatory Agent
Mechanism of Action (MOA)
SALAZO (Sulfasalazine) is a prodrug that is hydrolyzed by colonic bacteria into 5-aminosalicylic acid (5-ASA; Mesalamine) and sulfapyridine. 5-aminosalicylic acid is an inhibitor of prostaglandin biosynthesis. Moreover, sulfasalazine and / or its metabolites inhibit the release of inflammatory cytokines and TNF-α locally on the bowel. Also, SALAZO has beneficial systemic immunosuppressant effect.
Pharmacokinetics
- Bioavailability : Under 15% (sulfasalazine); 60% (sulfapyridine); 10-30% (5-ASA)
- Peak Plasma Time : 6 hours (sulfasalazine); 10 hours (sulfapyridine and 5-ASA)
- Protein Binding : More than 99% to albumin (sulfasalazine); 70% (sulfapyridine)
- Metabolism : Colonic bacteria
- Elimination Half-life : 10.4 to 14.8 hours (sulfapyridine)
- Excretion : Urine (systematically absorbed sulfapyridine and 5-ASA); faeces (majority of 5-ASA)
Indications and Dosage
Adults
- Ulcerative Colitis
Initially : Six to eight tablets of SALAZO per day in evenly divided doses with intervals no more than 8 hours; may initiate with two to four tablets of SALAZO per day to reduce gastrointestinal intolerance
Maintenance : Four tablets of SALAZO per day orally in evenly divided doses - Rheumatoid Arthritis
Initially :
1st week : One tablet of SALAZO once daily
2nd week : One tablet of SALAZO twice daily
3rd week : One tablet of SALAZO in the morning followed by two tablets of SALAZO in the evening
4th week : Two tablets of SALAZO three times a day
Daily dose may be increased up to SALAZO 3000 mg per day if clinical response is inadequate after 12 weeks - Crohn’s Disease (Off-label) : Six to twelve tablets of SALAZO per day in divided doses
Pediatric (safety and efficacy has not been established in children below 6 years of age) - Ulcerative Colitis
6 years or older
Initial : SALAZO 40 to 60 mg per kg per day divided every 4 to 8 hours
Maintenance : SALAZO 30 mg per kg per day divided every 6 hour - Juvenile Rheumatoid Arthritis
6 years or older : SALAZO 30 to 50 mg per kg per day in 2 equally divided doses
Maximum dose : SALAZO 2 gm per day
Administration : Take after meals. Administer in equally divided doses
Side Effects
GREATER THAN 10 % : Anorexia, headache, nausea, vomiting, gastric distress, apparently reversible oligospermia
RARE (LESS THAN 1 %) : Skin rash, pruritus, urticaria, fever, Heinz body anemia, hemolytic anemia, cyanosis
POST MARKETING REPORTS : Pseudomononucleosis, myocarditis, hepatotoxicity, elevated liver function tests, jaundice, cholestatic jaundice, cirrhosis, hepatitis, cholestasis and possible hepatocellular damage including liver necrosis and liver failure, Kawasaki-like syndrome, anaphylaxis, folate deficiency, nephrolithiasis, oropharyngeal pain, angioedema, purpura, pallor
Contraindications
Hypersensitivity to sulfasalazine or its metabolites, sulfonamides, or salicylates; intestinal or urinary tract obstruction; porphyria
Warnings / Precautions
- Caution in severe allergy or bronchial asthma.
- Blood dyscrasias and serious infections have been reported, including fatal sepsis, pneumonia and some infections were associated with agranulocytosis, neutropenia, or myelosuppression.
- Serious skin reactions have been reported such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.
- Severe hypersensitivity has been reported, including hepatitis, nephritis, myocarditis, mononucleosis like syndrome, hematological abnormalities and pneumonitis.
- Caution in anemia, gout, hepatic / renal impairment, hypochlorhydria, hypoprothrombinemia, thyrotoxicosis, vitamin K deficiency.
- Ensure adequate hydration to prevent crystalluria.
- May cause orange discoloration of the urine or skin.
- Some reports of bloody stools or diarrhoea in human milk fed infants of mothers taking sulfasalazine
Drug Interactions
- Sulfasalazine may potentiate the effects of coumarin anticoagulants.
- Sulfasalazine may potentiate the hypoglycemic effects of tolbutamide and chlorpropamide when used together.
- Concomitant use of anti-infectives may alter the action of sulfasalazine by altering intestinal flora and its metabolism.
- Sulfasalazine possibly decrease the absorption of digoxin.
- Sulfasalazine inhibits the absorption and metabolism of folic acid.
- Concomitant use of sulfasalazine and iron causes formation of iron chelates altering absorption and distribution of sulfasalazine.
Pregnancy Category : B but becomes D if used for prolonged periods or near term; increased potential for kernicterus in the newborn
Presentation
SALAZO 500 mg : A box of 10 blisters, each blister of 10 tablets