Sulfasalazine
Sulfasalazine is a synthetic salicylic acid derivative with an affinity for connective tissue containing elastin and formulated as a prodrug , antiinflammatory Sulfasalaine acts locally in the intestine through its active metabolite , sulfamide 5-aminosalicylic acid and salicylic acid , by a mechanism that is not clear ( Pubchem )
Salazopyrin En-Tabs 500 mg tablets also comes with Enteric coating to reduce GI SEs Typical regimen may start with 500 mg / day ↑ ed at intervals of 1 week by one 500 mg tablet a day to a max of 2-3 gm in divided doses
Ulcerative Colitis -induction and maintenance of remission Crohn’s disease – treatment Rheumatoid arthritis Sero negative spondylo-arthopathy ( including psoriatic arthritis and Psoriasis ) Can be used as monotherapy or in combination
Is a prodrug Structurally related to both salicylates ( for eg aspirin ) and sulphonamides Split by bacterial in colon into Sulfapyridine ( SP ) & Mesalazine MP ) Precise mechanism of action not know Local actions of mesalamine in colon – likely reason for effectiveness in inflammatory bowel dis RA- may be related to anti-inflammatory and immunomodulatory properties In rheumatoid arthritis a disease-modifying effect is seen in 1-3 months ( reduction in inflammatory markers ) Renal/Faecal- primary excretion routes
Adverse effects
Adverse reactions are possible to either Suphonamide or Salicylate Most commonly encountered are nausea , headache , rash , loss of appetite and raised temperature Few other points May discolour contact lenses ( yellow/ orange ) Can cause a fall in sperm count- leading to a reversible temporary decrease in male fertility Pregnancy- can be used not teratogenic Breast feeding – small amounts in milk ( risk neonatal haemolysis ) Patients with known ANA→ can induce lupus like illness G6PD ( glucose -6-phosphate dehydrogenase ) risk haemolytic anaemia
Digoxin- reduced absorption Hypoglycaemia risk ( if on hypoglycaemic agents ) Increased GI adverse effects -particularly nausea if used with Methotrexate Azathioprine / Mercaptopurine →bone marrow suppression and leucopenia
Monitoring- FBC or CBC Fortnightly for the 1st 3 months Monthly for 2nd 3 months 3 monthly or as clinically indicated after that WBC < 3.5 x 109 / L Neutrophils < 2 x 109 / L ( threshold may vary locally from 1.5 to 2 check with local team ) Platelets < 150 x 109 / L MCV > 105 fL ○ check Vit B12 and TSH ○ If abnormal treat underlying abnormality ○ If normal discuss with specialist team Withhold treatment until discussed with specialist team
LFT Fortnightly for the 1st 3 months Monthly for 2nd 3 months 3 monthly or as clinically indicated after that AST , ALT → twice upper limit of normal Withold treatment until discussed with specialist team
us and Es Renal function test Urinalysis Monthly for 1st 3 months As clinically indicated after that Excreted in urine and accumlation is associated with ↑risk of toxicity
Check for presence of rash or oral ulceration ( each visit ) Nausea / dizziness / headache Abnormal bruising , pallor , severe sore throat , fever malaise Unexplained acute widespread rash Oral ulceration
LINKS AND RESOURCES
PATIENT INFORMATION
Versus arthritis on sulfasalazine – a well written 8 page leaflet https://www.versusarthritis.org/media/12942/sulfasalazine-information-booklet-2019.pdf
Australian Rheumatology Association https://rheumatology.org.au/patients/documents/Sulfasalazine_2016_002.pdf
Medline Plus on Sulfasalazine https://medlineplus.gov/druginfo/meds/a682204.html
Medicine compendium on sulfasalazine https://www.medicines.org.uk/emc/files/pil.3838.pdf
American College of Rheumatology on Sulfasalazine https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Sulfasalazine-Azulfidine
Alberta rheumatology -concise PIL https://albertarheumatology.com/sulfasalazine/
A balanced well written informative page for patients from Health Navigator New Zealand https://www.healthnavigator.org.nz/medicines/s/sulfasalazine/
INFORMATION FOR CLINICIANS
BNF https://bnf.nice.org.uk/drug/sulfasalazine.html
A review article on DMARD monitoring Rigby WFC, Lampl K, Low JM, Furst DE. Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis Receiving Biologic or Nonbiologic DMARDs. Int J Rheumatol. 2017;2017:9614241. doi:10.1155/2017/9614241 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684575/
Another article on DMARD monitoring from BPAC NZ https://bpac.org.nz/BPJ/2008/October/dmards.aspx
FDA on sulfasalazine a 21-page document https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/007073s124lbl.pdf
Use of sulfasalazine in dermatology from DermNet Nz https://dermnetnz.org/topics/sulfasalazine/
A complete resource on sulfasalazine from PDR Net https://www.pdr.net/drug-summary/Azulfidine-sulfasalazine-1862
Drugbank database on sulfasalazine https://www.drugbank.ca/drugs/DB00795
References ;
- BSR/ BHPR guideline for disease-modifying anti-rheumatic drug ( DMARD ) therapy in consultation with the British Association of Dermatologists K Chakravarty et al Rhematology 2008 ; 1 of 16
- Gwent Shared Care Protocol Sulfasalazine for Rheumatoid Arthritis ABHB
- Drugbank accessed via http://www.drugbank.ca/drugs/DB00795
- CKS NKS accessed via http://cks.nice.org.uk/dmards#!scenario:11
- Shropshire Clinical Commissioning Group https://www.sath.nhs.uk/wp-content/uploads/2016/12/Sulfasalazine-Shropshire.pdf
- Wirral University Teaching Hospitals https://mm.wirral.nhs.uk/document_uploads/shared-care/SulfasalazineRheumatologysharedcare7513.pdf