Sulfasalazine Folic acid

Patients receiving sulfasalazine should receive oral folic acid supplementation since sulfasalazine inhibits folic acid absorption. 

Drugs that may interact with folic acid include aminosalicylic acid, oral contraceptives, dihydrofolate reductase inhibitors (eg, methotrexate, trimethoprim), sulfasalazine, hydantoins. 

Drugs that may interact with sulfasalazine include digoxin, sulfonylureas, folic acid, cyclosporine, methotrexate, thiopurines, and warfarin. 

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbutamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives. 

Since sulfasalazine inhibits the absorption of folic acid, patients may become folate deficient during longterm therapy. Sulfasalazine decreases the bioavailabiUty of digoxin. Cholestyramine reduces the metabolism of sulfasalazine. Sulfasalazine causes a reversible decrease in sperm counts. Sulfasalazine is safe in pregnancy. 

Sulfasalazine has a high incidence of adverse effects, most of which are attributable to systemic effects of the sulfapyridine molecule. Slow acetylators of sulfapyridine have more frequent and more severe adverse effects than fast acetylators. Up to 40% of patients cannot tolerate therapeutic doses of sulfasalazine. The most common problems are dose-related and include nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise. Hypersensitivity to sulfapyridine (or, rarely, 5-ASA) can result in fever, exfoliative dermatitis, pancreatitis, pneumonitis, hemolytic anemia, pericarditis, or hepatitis. Sulfasalazine has also been associated with oligospermia, which reverses upon discontinuation of the drug. Sulfasalazine impairs folate absorption and processing hence, dietary supplementation with 1 mg/d folic acid is recommended. 

Antibiotics. Long-term administration of antibiotics could lead to vitamin B6 deficiency, If symptoms of peripheral neuropathy develop (numbness and tingling of the extremities), administer vitamin B6. Sulfasalazine can decrease the absorption of folic acid, and trimethoprim can cause folate deficiency, hence the need to administer folic acid if there is evidence of deficiency. Rifampicin can cause disturbances in vitamin D metabolism and lead to osteomalacia. The absorption of tetracyclines can be reduced by calcium, magnesium, iron and zinc, while this antibiotic could also decrease the absorption of these minerals. This effect is probably least with minocycline and is not confirmed with doxycycline. Doses of minerals and antibiotic should be separated by at least 2 hours. The absorption of quinolones is reduced by cationic and anionic supplements. 

Sulfasalazine reduces folic acid absorption, but rarely to a chnically significant extent, although megaloblastic anemia has rarely been documented (51,52). 

Clinically important, potentially hazardous interactions with acitretin, aldesleukin, aminoglycosides, amiodarone, amoxicillin, ampicillin, aspirin, bacampicillin, bismuth, carbenicillin, chloroquine, cisplatin, cloxacillin, co-trimoxazole, dapsone, demeclocycline, dexamethasone, diclofenac, dicloxacillin, etodolac, etoricoxib, etretinate, fenoprofen, flurbiprofen, folic acid antagonists, haloperidol, hydrocortisone, ibuprofen, indomethacin, influenza vaccines, ketoprofen, ketorolac, lithium, magnesium trisalicylate, meclofenamate, mefenamic acid, methicillin, mezlocillin, minocycline, nabumetone, nafcillin, naproxen, NSAIDs, omeprazole, oxacillin, oxaprozin, oxytetracycline, paromomycin, penicillin G, penicillin V, penicillins, phenylbutazone, piperacillin, piroxicam, polypeptide antibiotics, prednisolone, prednisone, probenecid, procarbazine, rofecoxib, salicylates, salsalate, sapropterin, sulfadiazine, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfisoxazole, sulindac, tazobactum, tenoxicam, tetracycline, ticarcillin, tolmetin, trimethoprim, vaccines... 

Vitamin status also may be affected by drugs (Table 135-15). For example, sulfasalazine therapy has been noted to cause a decrease in folic acid, isoniazid therapy causes pyridoxine deficiency, and furosemide therapy may result in decreased thiamin concentrations. Furthermore, some drug therapy outcomes may be affected by vitamin intake. The ingestion of megadoses of folic acid may decrease methotrexate s therapeutic effect, whereas changes in an individual s usual vitamin K intake may cause variability in warfarin s anticoagulation effects. 

Sulfasalazine may reduce GI absorption of digoxin and folic acid. 

There is an increased risk of diarrhea in patients taking misoprostol with the m nesium-containing antacids. Sulfasalazine may increase the risk of toxicity of oral hypoglycemic dru, zidovudine, methotrexate, and phenytoin. There is an increased risk of crys-talluria when sulfasalazine is administered with medienamine. A decrease in the absorption of iron and folic acid may occur when these ents are administered with sulfasalazine. When bismuth subsalicylate is administered witli aspirin-containing dru, there is an increased risk of salicylate toxicity. There is an increased risk of toxicity of valproic acid and methotrexate and decreased effectiven s of the corticosteroids when these agents are administered with bismuth subsalicylate. 

The absorption of folic acid was reduced by about one-third (from 65 to 44.5%) in patients with ulcerative and granulomatous colitis, when compared with healthy subjects, and even further reduced (down to 32%) when sulfasalazine was taken. Another study confirmed that serum folate levels are lower in patients with ulcerative colitis taking sulfasalazine, and that the impairment of the absorption of folates by sulfasalazine was a mechanism in this. Sulfasalazine is also known to interfere with folate metabolism. 

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