Sulfasalazine
EN-Tablet
Category:
Bowel disease (inflammatory) suppressant; antirheumatic (disease-modifying) (USPDI)
Chemistry:
sulfasalazine 500 mg EN-tablets.
4-hydroxy-4'- (2-pyridylsulfamoyl)azobenzene-3-carboxylic acid
C18H14N4O5S = 398.4
Pharmacokinetics:
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Absorption
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Poorly absorbed; approximately 20%
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Distribution
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Distributed to serum, connective
tissue, serous fluids, liver and intestinal wall.
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Protein binding
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Very high ( approximately 99%)
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Biotransformation
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Unabsorbed: Cleaved in the colon
by intestinal bacteria to form sulfapyridine and mesalamine.
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Half-life
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5 to 10 hours
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Elimination
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Fecal: trace amounts
Renal: approximately 75 to 91%
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Indications
- Ulcerative colitis
- Active crohn's disease
Off-label uses:
- Multiple sclerosis
- Psoriasis (www.medicines.org.uk & Drug Facts & BNF)
Contraindications:
- 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
- Intestinal or urinary obstruction (USPDI & BNF & www.medicines.org.uk)
Warnings & Precautions:
- 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. Assessment of renal function (including urinalysis) should be performed in all patients initially and at least monthly for the first three months of treatment. 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.
- Sulfasalazine should be given with caution to patients with severe allergy or bronchial asthma.
- Since 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).
- Because sulfasalazine causes crystalluria and kidney stone formation, adequate fluid intake should be ensured during treatment.
- Oligospermia and infertility may occur in men treated with sulfasalazine. Discontinuation of the drug appears to reverse these effects within 2 to 3 months. (www.medicines.org.uk & USPDI)
Pregnancy and Breast – feeding:
FDA Pregnancy Category: B
Pregnancy
Reproduction studies in rats and rabbits have revealed no evidence of harm to the fetus. 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. Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency. 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 diarrhoea in infants who were breastfeeding from mothers on sulfasalazine. In cases where the outcome was reported, bloody stools or diarrhoea resolved in the infant after discontinuation of sulfasalazine in the mother. (www.medicines.org.uk)
Drug Interactions:
Cardiac glycosides, Heparin, Heparin (low molecular weight), Methotrexate, Methylfolate, Nitric oxide, Prilocaine, Thiopurine analogs, Varicella virus containing vaccines, Folic acid, Phenylbutazone, Sulfinpyrazone, Dong quai, St John's wort. (Drug Facts & USPDI)
Adverse Reactions:
Common: anaemia (incl. respective laboratory parameters), dizziness, headache, eye haemorrhage (incl. conjunctival haemorrhage), hypotension, haematoma, epistaxis, haemoptysis, gingival bleeding, gastrointestinal tract haemorrhage (incl. rectal haemorrhage), gastrointestinal and abdominal pains, dyspepsia, nausea, constipation, diarrhoea, vomiting, pruritus (incl. uncommon cases of generalised pruritus), rash, ecchymosis, cutaneous and subcutaneous haemorrhage, pain in extremity, urogenital tract haemorrhage (incl. haematuria and menorrhagia), renal impairment (incl. blood creatinine increased, blood urea increased), fever, peripheral oedema, decreased general strength and energy (incl. fatigue and asthenia), increase in transaminases, postprocedural haemorrhage (incl. postoperative anaemia, and wound haemorrhage), contusion, wound secretion; Uncommon: thrombocythemia (incl. platelet count increased), allergic reaction, dermatitis allergic, cerebral and intracranial haemorrhage, syncope, tachycardia, dry mouth, hepatic function abnormal, urticaria, haemarthrosis, feeling unwell (incl. malaise), increased bilirubin, increased blood alkaline phosphatase, increased LDH, increased lipase, increased amylase, increased GGT; Rare: jaundice, muscle haemorrhage, localised oedema, bilirubin conjugated increased (with or without concomitant increase of ALT), vascular pseudoaneurysm; Not known: compartment syndrome secondary to a bleeding, renal failure/acute renal failure secondary to a bleeding sufficient to cause hypoperfusion. (www.medicines.org.uk)
OVERDOSE:
The drug has low acute per oral toxicity in the absence of hyper-sensitivity. There is no specific antidote and treatment should be supportive.
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate) - not necessarily inclusive:
Anuria, crystalluria or hematuria (blood in urine; lack of urination, lower back pain; pain or burning while urinating); drowsiness; gastrointestinal disturbances (abdominal or stomach pain or upset; diarrhea; loss of appetite; nausea or vomiting); seizures.
Treatment of overdose:
To decrease absorption: The stomach may be emptied by inducing emesis with ipecac syrup (taking care to guard against aspiration) or by gastric lavage.
To enhance elimination: The urine may be alkalinized and, if kidney function is normal, fluids forced. If anuria is present, fluids and salt should be restricted. Catheterization of the ureters may be indicated when there is complete renal blockage by crystals. The low molecular weight of sulfasalazine and its metabolites may facilitate removal by dialysis. (www.medicines.org.uk & USPDI)
DOSAGE AND ADMINISTRATION:
EN-Tablets should be used where there is gastro-intestinal intolerance of plain tablets. They should not be crushed or broken.
Elderly Patients: No special precautions are necessary.
Adults
Ulcerative colitis
Initial dosage: 3 to 4 g/day in evenly divided doses with dosage intervals not exceeding 8 hours. It may be advisable to initiate therapy with a lower dosage (eg, 1 to 2 g/day) to reduce possible GI intolerance. If symptoms of gastric intolerance occur after the first few doses, they may be alleviated by having the daily dose and subsequently increasing it gradually over several days. If gastric intolerance continues, stop therapy for 5 to 7 days, then reintroduce at a lower daily dose.
Maintenance dosage: 2 g/day. If dosages exceeding 4 g/day are required to achieve the desired therapeutic effect, keep in mind the increased risk of toxicity.
Children
Ulcerative colitis
6 years and older
Initial dosage: 40 to 60 mg/kg/day, divided into 3 to 6 doses. If symptoms of gastric intolerance occur after the first few doses, they may be alleviated by having the daily dose and subsequently increasing it gradually over several days. If gastric intolerance continues, stop therapy for 5 to 7 days, then reintroduce at a lower daily dose.
Maintenance dosage: 30 mg/kg/day, divided into 4 doses. (www.medicines.org.uk)
Storage:
Store at 25°C; excursions are permitted between 15° and 30°C. (USPDI)