Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Rosemont Pharmaceuticals Ltd, Rosemont House, Yorkdale Industrial Park, Braithwaite Street, Leeds, LS11 9XE, UK
Sulfasalazine is contraindicated in:
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. Please see Section 4.4 “Interference with laboratory testing”.
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.
Use in children with the concomitant condition systemic onset juvenile rheumatoid arthritis may result in a serum sickness like reaction; therefore sulfasalazine is not recommended in these patients.
Since sulfasalazine may cause haemolytic anaemia, it should be used with caution in patients with glucose-6-phosphate dehydrogenase 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.
Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of sulfasalazine. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment. If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, sulfasalazine treatment should be discontinued. The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis. If the patient has developed SJS or TEN with the use of sulfasalazine, sulfasalazine must not be re-started in this patient at any time.
Sulfasalazine may colour the urine orange-yellow.
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.
Sulfasalazine or its metabolites may interfere with ultraviolet absorbance, particularly at 340 nm, and may cause interference with some laboratory assays that use NAD or NADP to measure ultraviolet absorbance around that wavelength. Examples of such assays may include urea, ammonia, LDH, α-HBDH and glucose. It is possible that alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase-muscle/brain (CK-MB), glutamate dehydrogenase (GLDH), or thyroxine may also show interference when sulfasalazine treatment is given at high doses. Consult with the testing laboratory regarding the methodology used. Caution should be exercised in the interpretation of these laboratory results in patients who are receiving sulfasalazine. Results should be interpreted in conjunction with clinical findings.
This product contains small amounts of ethanol (alcohol), less than 100mg per 5ml.
Certain types of extended wear soft contact lenses may be permanently stained during therapy.
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 by sulfasalazine, bone marrow suppression and leucopenia have been reported when the thiopurine 6-mercaptopurine or its prodrug, azathioprine, and oral sulfasalazine were used concomitantly.
Co-administration 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.
Reproduction studies in rats and rabbits have revealed no evidence of harm to the foetus. 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 foetal 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.
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 of 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.
No specific effects.
Overall, about 75% of ADRs occur within three months of treatment and over 90% by six months. Some unwanted effects are dose-dependent and symptoms can often be alleviated by reduction of the dose.
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.
The adverse reactions observed during clinical studies conducted with Sulfasalazine have been provided in a single list below by class and frequency (very common (≥1/10); common (≥1/100 to< 1/10); uncommon (≥1/1000 to < 1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000)). Where an adverse reaction was seen at different frequencies in clinical studies, it was assigned to the highest frequency reported.
Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in the list below.
Not known: Pseudomembranous colitis
Common: Leukopenia
Uncommon: Thrombocytopenia*
Not known: Agranulocytosis, aplastic anemia, haemolytic anemia, Heinz body anaemia, hypoprothrombinaemia, lymphadenopathy, macrocytosis, megaloblastic anemia, methaemoglobinaemina, neutropenia, pancytopenia
Not known: Anaphylaxis, polyarteritis nodosa, serum sickness
Not known: Loss of appetite
Common: Insomnia
Uncommon: Depression
Not known: Hallucinations
Common: Dizziness, headache, taste disorders
Uncommon: Convulsions
Not known: Aseptic meningitis, ataxia, encephalopathy, peripheral neuropathy, smell disorders
Common: Tinnitus
Uncommon: Vertigo
Common: Conjuctivial and scleral injection
__Not known: Allergic myocarditis, cyanosis, pericarditis
Uncommon: Vasculitis
Common: Cough
Uncommon: Dyspnoea
Not known: Fibrosing alveolitis, eosinophilic infiltration, interstitial lung disease
Very Common: Gastric distress, nausea
Common: Abdominal pain, diarrhoea, vomiting, stomatitis
Not known: Aggravation of ulcerative colitis, pancreatitis, parotitis
Not known: Hepatic failure, fulminant hepatitis, hepatitis*
Common: Pruritus
Uncommon: Alopecia, urticaria
Very rare: Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (see section 4.4)
Not known: Epidermal necrolysis (Lyell’s syndrome), Drug rash with eosinophilia and systemic symptoms (DRESS), toxic pustuloderma, erythema, exanthema, exfoliative dermatitis, periorbital oedema, lichen planus, photosensitivity
Common: Arthralgia
Not known: Systemic lupus erythematosus
Common: Proteinuria
Not known: Nephrotic syndrome, interstitial nephritis, crystalluria*, haematuria
Not known: Reversible oligospermia*
Common: Fever
Uncommon: Facial oedema
Not known: Yellow discoloration of skin and body fluids
Uncommon: Elevation of liver enzymes
Not known: Induction of autoantibodies
* See Section 4.4 for further information
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
None relevant.
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