IN INFLAMMATORY BOWEL DISEASE THE USUAL INITIAL ADULT DOSE OF SULFASALAZINE IS 1 TO 2 G BY MOUTH 4 TIMES DAILY IN THE UK. HOWEVER, DOSES OVER 4 G DAILY ARE ASSOCIATED WITH AN INCREASED RISK OF TOXICITY, AND IN THE USA, THEREFORE, THE USUAL DOSE IS 1 G GIVEN 3 OR 4 TIMES DAILY, AND AN INITIAL DOSE OF 500 MG EVERY 6 TO 12 HOURS MAY BE RECOMMENDED TO LESSEN GASTROINTESTINAL ADVERSE EFFECTS. ENTERIC-COATED TABLETS ARE ALSO CLAIMED TO REDUCE THE INCIDENCE OF ADVERSE GASTROINTESTINAL EFFECTS. THE OVERNIGHT INTERVAL BETWEEN DOSES SHOULD NOT EXCEED 8 HOURS. ON REMISSION THE DOSE IN PATIENTS WITH ULCERATIVE COLITIS IS GRADUALLY REDUCED TO 2 G DAILY AND THEN GENERALLY CONTINUED INDEFINITELY. FOR CHILDREN 2 YEARS OF AGE OR OLDER DOSES SHOULD BE PROPORTIONAL TO BODY-WEIGHT; INITIALLY 40 TO 60 MG/KG MAY BE GIVEN DAILY IN DIVIDED DOSES REDUCED TO 20 TO 30 MG/KG DAILY FOR THE MAINTENANCE OF REMISSION.
SULFASALAZINE IS ALSO GIVEN RECTALLY, AS SUPPOSITORIES, INITIALLY AT A DOSE OF 1 G AT NIGHT AND IN THE MORNING. AFTER THREE WEEKS THE DOSAGE IS GRADUALLY REDUCED ACCORDING TO RESPONSE. RECTAL SULFASALAZINE CAN BE GIVEN AS 0.5 TO L G NIGHT AND MORNING AS AN ADJUNCT TO TREATMENT BY MOUTH. SULFASALAZINE MAY ALSO BE GIVEN BY ENEMA IN A DOSE OF 3 G AT BEDTIME. THE BNFC SUGGESTS THE FOLLOWING DAILY DOSAGE MAY BE GIVEN IN DIVIDED DOSES TO CHILDREN AS SUPPOSITORIES ACCORDING TO AGE: 5 TO 8 YEARS OLD: 1 G; 8 TO 12 YEARS OLD: 1.5 G; 12 TO 18 YEARS OLD: 2 G. ENEMAS, TO BE RETAINED FOR AT LEAST 1 HOUR, MAY BE GIVEN AT NIGHT IN DOSES OF 1 TO 1.5 G FOR CHILDREN AGED 2 TO 7 YEARS, 1.5 TO 2.25 G FOR CHILDREN AGED 7 TO 12 YEARS, AND 3 G FOR CHILDREN 12 TO 18 YEARS.
IN ADULT RHEUMATOID ARTHRITIS TREATMENT IS USUALLY STARTED WITH A DOSE OF 500 MG DAILY BY MOUTH, AS ENTERIC-COATED TABLETS, FOR THE FIRST WEEK; DOSAGE IS THEN INCREASED BY 500 MG DAILY EACH WEEK TO A MAXIMUM OF 3 G DAILY GIVEN IN 2 TO 4 DIVIDED DOSES ACCORDING TO TOLERANCE AND RESPONSE. IN THE USA, SULFASALAZINE CAN ALSO BE USED FOR POLYARTICULAR JUVENILE RHEUMATOID ARTHRITIS IN CHILDREN AGED 6 YEARS AND OLDER WHO HAVE NOT RESPONDED ADEQUATELY TO SALICYLATES OR OTHER NSAIDS. A DOSE OF 30 TO 50 MG/KG DAILY IS GIVEN IN TWO DIVIDED DOSES, TO A MAXIMUM DOSE OF 2 G DAILY. TO REDUCE ADVERSE GASTROINTESTINAL EFFECTS, AN ENTERIC-COATED TABLET IS USED AND THE INITIAL DOSE SHOULD BE A QUARTER TO A THIRD OF THE PLANNED MAINTENANCE; IT IS THEN INCREASED WEEKLY TO REACH THE MAINTENANCE DOSE AFTER ONE MONTH. ALTHOUGH SULFASALAZINE IS NOT LICENSED FOR JUVENILE RHEUMATOID ARTHRITIS IN THE UK, THE BNFC SUGGESTS THAT CHILDREN AGED 2 TO 18 YEARS ARE GIVEN AN INITIAL ORAL DOSE OF 5 MG/KG TWICE DAILY FOR 1 WEEK. THE DOSE IS THEN INCREASED TO 10 MG/KG TWICE DAILY FOR 1 WEEK, THEN 20 MG/KG TWICE DAILY FOR 1 WEEK, AND MAINTAINED ON A DOSE OF 20 TO 25 MG/KG TWICE DAILY. FOR CHILDREN AGED 2 TO 12 YEARS THE MAXIMUM DOSE SUGGESTED IS 2 G DAILY, AND FOR CHILDREN AGED 12 TO 18 YEARS 3 G DAILY.
PSORIASIS.
IN A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY INVOLVING 50 PATIENTS WITH MODERATE TO SEVERE PLAQUE-TYPE PSORIASIS, SULFASALAZINE 3 TO 4 G DAILY PRODUCED A SIGNIFICANTLY GREATER CLINICAL IMPROVEMENT THAN PLACEBO AFTER 4 WEEKS OF TREATMENT WITH A FURTHER IMPROVEMENT AT 8 WEEKS.
RHEUMATOID ARTHRITIS.
SULFASALAZINE IS CONSIDERED TO BE A USEFUL DISEASE-MODIFYING ANTIRHEUMATIC DRUG (DMARD) IN THE TREATMENT OF RHEUMATOID ARTHRITIS. STUDIES HAVE FOUND A BENEFICIAL CLINICAL EFFECT OF SULFASALAZINE, COMPARED WITH PLACEBO, ON TENDER AND SWOLLEN JOINTS, PAIN, AND ERYTHROCYTE SEDIMENTATION RATE. META-ANALYSES OF GENERALLY SHORT-TERM COMPARATIVE STUDIES SUGGEST THAT SULFASALAZINE IS ROUGHLY COMPARABLE IN EFFICACY TO METHOTREXATE, INTRAMUSCULAR GOLD (SODIUM AUROTHIOMALATE), AND PENICILLAMINE. OTHER REVIEWS HAVE ALSO SUGGESTED THAT IT MAY HAVE SIMILAR EFFICACY TO HYDROXYCHLOROQUINE AND LEFLUNOMIDE. ALTHOUGH THERE ARE REGIONAL DIFFERENCES IN THE PRESCRIPTION OF DMARDS, SULFASALAZINE HAS BEEN WIDELY USED FOR INITIAL THERAPY, ESPECIALLY OF LESS SEVERE DISEASE. IN AN OPEN STUDY OF 200 PATIENTS WITH RHEUMATOID ARTHRITIS WHO WERE RANDOMLY ALLOCATED TO TREATMENT WITH SULFASALAZINE OR AURANOFIN, 31% OF THE SULFASALAZINE RECIPIENTS WERE STILL TAKING THE DRUG AFTER 5 YEARS COMPARED WITH 15% OF AURANOFIN RECIPIENTS. IMPROVEMENT OVER BASELINE WAS STILL SIGNIFICANT AT 5 YEARS FOR THOSE PATIENTS RECEIVING SULFASALAZINE BUT NOT IN THOSE TREATED WITH AURANOFIN. ALTHOUGH ONE STUDY FAILED TO FIND CONVINCING EVIDENCE THAT USING SULFASALAZINE WITH METHOTREXATE WAS MORE EFFECTIVE THAN EITHER DRUG ALONE, OTHER STUDIES HAVE SHOWN THAT COMBINATION TREATMENT WITH SULFASALAZINE PLUS METHOTREXATE AND HYDROXYCHLOROQUINE WAS MORE EFFECTIVE THAN METHOTREXATE ALONE OR WITH SULFASALAZINE OR HYDROXYCHLOROQUINE OR THE COMBINATION OF SULFASALAZINE WITH HYDROXYCHLOROQUINE. A REVIEW OF SULFASALAZINE USE IN THE MANAGEMENT OF RHEUMATOID ARTHRITIS CONCLUDED THAT COMBINATION THERAPY MAY BE OF BENEFIT IN PATIENTS WITH EARLY OR ADVANCED RHEUMATOID ARTHRITIS BUT THAT THERE IS STILL A NEED FOR STUDIES TO DETERMINE THE EFFICACY AND TOLERABILITY OF VARIOUS COMBINATIONS.