Salazopyrin

/ Pfizer

The dosage of Salazopyrin® should be individually adjusted according to the patient’s tolerance and response to treatment.
EN-tabs must be swallowed intact, preferably after meals, and should not be crushed or broken.
Elderly Patients: No special precautions are necessary.
Ulcerative colitis
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.
Night-time interval between doses should not exceed 8 hours.
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 four fold 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
Crohn’s Disease
In active Crohn’s Disease, Salazopyrin® should be administered as in attacks ofulcerative colitis (see above).

Treatment of ulcerative colitis and Crohn’s disease.

Infants under the age of 2 years.
Patients with known hypersensivity to sulfasalazine, its metabolites, or any other component of the product as well as sulfonamides, or salicylates.
Patients with Porphyria.

* Serious infections associated with myelosuppression, including sepsis and pneumonia, have been reported. Patients who develop a new infection while undergoing treatment with sulfasalazine should be monitored closely. Administration of sulfasalazine should be discontinued if a patient develops a serious infection. Caution should be exercised when considering the use of sulfasalazine in patients with a history of recurring or chronic infections or with underlying conditions which may predispose patients to infections.
* Complete blood counts, including differential white cell count, and liver function tests, should be performed before starting sulfasalazine and every second week during the first three months of therapy. During the second three months, the same tests should be done once monthly and thereafter once every three months, and as clinically indicated. Baseline assessment of renal function (including urinalysis) is required to be performed in all patients initiating treatment with sulfasalazine. For patients with baseline renal impairment, treatment with sulfasalazine should only be initiated if the benefits are considered to outweigh risk. Thereafter, periodic renal function monitoring, especially in the early months of treatment, should be conducted based on clinical judgment taking baseline renal function into account. Treatment should be discontinued if renal function deteriorates. The patient should also be counselled to report immediately with the presence of clinical signs such as sore throat, fever, pallor, purpura, jaundice, malaise or unexpected non-specific illness during sulfasalazine treatment, this may indicate myelosuppression, hemolysis, or hepatotoxicity. Treatment should be stopped immediately while awaiting the results of blood tests.
* Should not be given to patients with impaired hepatic function or with blood dyscrasias, unless the potential benefit outweighs the risk.
* Should be given with caution to patients with severe allergy or bronchial asthma.
* Severe hypersensitivity reactions may include internal organ involvement, such as hepatitis, nephritis, myocarditis, mononucleosis-like syndrome (i.e., pseudomononucleosis), hematological abnormalities (including hematophagic histiocytosis), and/or pneumonitis including eosinophilic infiltration.
* Severe, life-threatening, systemic hypersensitivity reactions such as Drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in patients. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately.
* Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of sulfasalazine. Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first month of treatment. Sulfasalazine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
* Sulfasalazine may cause haemolytic anaemia, it should be used with caution in patients with G-6-PD deficiency.
* Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency, potentially resulting in serious blood disorders (e.g., macrocytosis and pancytopenia). This can be normalised by administration of folic acid or folinic acid (leucovorin).
* Crystalluria and kidney stone formation may occur, adequate fluid intake must be maintained.
* Oligospermia and infertility may occur in men treated with sulfasalazine. Discontinuation of the drug appears to reverse these effects within 2 to 3 months.
* Several reports of possible interference with measurements, by liquid chromatography, of urinary normetanephrine causing a false-positive test result have been observed in patients exposed to sulfasalazine or its metabolite, mesalamine/ mesalazine.
See prescribing information for full details.

Overall, about 75% of ADRs occur within 3 months of starting therapy, and over 90% by 6 months. Some undesirable effects are dose-dependent and symptoms can often be alleviated by reduction of the dose.
General: Sulfasalazine is split by intestinal bacteria to sulfapyridine and 5-amino salicylate so ADRs to either sulfonamide or salicylate are possible. Patients with slow acetylator status are more likely to experience ADRs related to sulfapyridine. The most commonly encountered ADRs are nausea, headache, rash, loss of appetite and raised temperature.
Very common: Gastric distress, Nausea
Common: Leukopenia, Loss of appetite, Insomnia, Dizziness, Headache, Taste disorders, Tinnitus, Cough, Abdominal pain, Diarrhea, Vomiting, Stomatitis, Pruritus, purpura, Arthralgia, Proteinuria, Fever.
See prescribing information for full details.

Reduced absorption of digoxin, resulting in non-therapeutic serum levels, has been reported when used concomitantly with oral sulfasalazine Sulfonamides bear certain chemical similarities to some oral hypoglycemic agents. Hypoglycemia has occurred in patients receiving sulfonamides. Patients receiving sulfasalazine and hypoglycemic agents should be closely monitored.
Due to inhibition of thiopurine methyltransferase (TPMT) by sulfasalazine, bone marrow suppression and leucopenia have been reported when the thiopurine 6-mercaptopurine or its 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.

Pregnancy:Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency. There have been reports of babies with neural tube defects born to mothers who were exposed to sulfasalazine during pregnancy, although the role of sulfasalazine in these defects has not been established. 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. Patients should avoid breastfeeding while taking this medicine.
There have been reports of bloody stools or diarrhea in infants who were breastfeeding from mothers on sulfasalazine. In cases where the outcome was reported, bloody stools or diarrhea resolved in the infant after discontinuation of sulfasalazine in the mother.

The drug has low acute per oral toxicity in the absence of hypersensitivity. There is no specific antidote and treatment should be supportive.

Storage: Store below 25°C. Bottles: After first opening can be used for 6 months in room temperature under 25ºC.