Brand name: Salazopyrin
Active ingredient (generic name): Sulfasalazine
Manufacturer: Pfizer
Importer: Behestan Darou
Pharmacotherapeutic group: anti- inflammatory
Pharmaceutical form: 500mg tablets
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Around 90% of a dose reaches the colon where bacteria split the drug into sulfapyridine (SP) and mesalazine (ME). These are active, and the unsplit sulfasalazine (SASP) is also active on a variety of symptoms. Overall the drug and its metabolites exert immunomodulatory effects, antibacterial effects, effects on the arachidonic acid cascade and alteration of activity of certain enzymes. The net result clinically is a reduction in activity of the inflammatory bowel disease. The enteric coated SASP is registered for the treatment of rheumatoid arthritis, where the effect resembles penicillamine or gold. |
Pharmacokinetic:
For SASP given as a single 3g oral dose, peak serum levels of SASP occurred in 3-5 hours, elimination half life was 5.7 ±0.7 hours, lag time 1.5 hours. Free SP first appears in plasma in 4.3 hours after a single dose with an absorption half life of 2.7 hours. The elimination half life was calculated as 18 hours. Turning to mesalazine, in urine only AC-ME (not free ME) was demonstrable, the acetylation probably largely achieved in the colon mucosa. After a 3g SASP dose lag time was 6.1 ±2.3 hours and plasma levels kept below 2µg/ml total ME. Urinary excretion half-life was 6.0 ±3.1 hours and absorption half life based on these figures 3.0 ±1.5 hours. Renal clearance constant was 125 ml/min corresponding to the GFR.
Therapeutic indication:
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In Induction and maintenance of remission of ulcerative colitis; treatment of active Crohn's Disease. |
Dosage and administration:
Adults
Severe Attacks: Salazopyrin 2-4 tablets four times a day may be given in conjunction with steroids as part of an intensive management regime. Rapid passage of the tablets may reduce effect of the drug.
Moderate Attack: 2-4 tablets four times a day may be given in conjunction with steroids.
Maintenance Therapy: With induction of remission reduce the dose gradually to 4 tablets per day. This dosage should be continued indefinitely since discontinuance even several years after an acute attack is associated with a fourfold increase in risk of relapse.
Children
The dose is reduced in proportion to body weight.
Acute Attack or Relapse: 40-60mg/kg per day
Maintenance Dosage: 20-30mg/kg per day
Salazopyrin Suspension may provide a more flexible dosage form.
Adverse reaction:
The most commonly encountered ADRs are nausea, headache, rash, loss of appetite and raised temperature.
Other undesirable effects associated with Salazopyrin administration are Leukopenia, Insomnia, Dizziness, Taste Disorders, Tinnitus, Conjunctiva and sclera injection, cough, Gastric distress, nausea, Abdominal pain, diarrhea, vomiting, Stomatitis, Pruritus, Arthralgia and fever.
Contraindication:
Sulfasalazine is contraindicated in:
- Infants under the age of 2 years
- Patients with a known hypersensitivity to sulfasalazine, its metabolites or any of the excipients as well as sulfonamides or salicylates
- Patients with porphyria
Pharmacokinetic interactions:
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Reduced absorption of digoxin, resulting in non-therapeutic serum levels, has been reported when used concomitantly with oral sulfasalazine. Due to inhibition of thiopurine methyltransferase by salazopyrin, bone marrow suppression and leucopenia have been reported when the thiopurine 6-mercaptopurine or it's prodrug, azathioprine, and oral salazopyrin were used concomitantly. Coadministration of oral sulfasalazine and methotrexate to rheumatoid arthritis patients did not alter the pharmacokinetic disposition of the drugs. However, an increased incidence of gastrointestinal adverse events, especially nausea, was reported. |
Special warnings:
Complete blood counts (including differential white cell count), liver function tests and assessment of renal function (including urinalysis) should be performed in all patients before starting therapy with sulfasalazine, and frequently during the first 3 months of therapy. Thereafter, monitoring should be performed as clinically indicated. The patient should also be counselled to report immediately with any sore throat, fever, malaise, pallor, purpura, jaundice or unexpected non-specific illness during sulfasalazine treatment, this may indicate myelosuppression, haemolysis or hepatoxicity. Treatment should be stopped immediately while awaiting the results of blood tests. .
Sulfasalazine should not be given to patients with impaired hepatic or renal function or with blood dyscrasias, unless the potential benefit outweighs the risk.
Because sulfasalazine causes crystalluria and kidney stone formation, adequate fluid intake should be ensured during treatment.
Pregnancy and lactation:
Pregnancy: Published data regarding use of sulfasalazine in pregnant women have revealed no evidence of teratogenic hazards. If sulfasalazine is used during pregnancy, the possibility of fetal harm appears remote. Because the possibility of harm cannot be completely ruled out, sulfasalazine should be used during pregnancy only if clearly needed.
Lactation: Sulfasalazine and sulfapyridine are found in low levels in breast milk. Caution should be used, particularly if breastfeeding premature infants or those deficient in G-6-PD.
Storage temperature:
Room temperature (15-25 C)
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