Haematological changes in a patient on long-term treatment with a trimethoprim-sulphonamide combination

Combination of Folic Acid and Folinic Acid Antagonists in Human and Veterinary Medicine

“…Hematological disturbances were noted in 0.38% of these 20,000 cases: leuko-, neutro-and trombocytopenias, mostly laboratory findings without clinical symptoms (table IV). Megaloblastic anemia was recorded in two cases [13,24]. All these changes were reversible.…”

Transient erythroid hypoplasia in a patient on long-term co-trimoxazole therapy

“…reduced folate), although co-trimoxazole therapy continued, suggesting impairment of folate utilization due to trimethoprim via its action on dihydrofolate reductase. Jewkes, Edwards and Grant (1971) reported in detail a patient who developed megaloblastic ery-thropoiesis 6 months after starting the currently recommended dose of trimethoprim 320 mg combined with sulphamethoxazole 1600 mg daily, to suppress bronchial infection. Folic acid therapy was of no avail, but there was a dramatic response to folinic acid, again indicating a block in folate metabolism at the level of dihydrofolate reductase.…”

Folate Status during Long-Term Therapy with Trimethoprim and Sulphadiazine

“…However, such an effect could not be disclosed. Other authors [5,11,12] have previously observed signs of megaloblastic anaemia; this anaemia seems to be due either to very large doses of the drugs [12] or to toxic accumulation of tri methoprim because of renal insufficiency [13], However, aggravation of megaloblas tic anaemia during the treatment with tri methoprim and sulphonamide was reported by Chanarin and England [4], It will there fore be reasonable to make sure that folate deficiency is not present before long-term combination therapy is started.…”

“…Some in vestigators have observed the development of megaloblastic anaemia in association with this combination therapy [5,11,12], but in most cases the haematological side ef fects were mild and reversible.…”