Can losartan cause anemia?/nA 69-year-old woman with hypertension is treated with losartan, dose un

Fråga: Can losartan cause anemia?

A 69-year-old woman with hypertension is treated with losartan, dose unknown. Other drug used is metoprolol. Five months after initiation of losartan treatment her Hb value was within the normal range (120-150 g/l). About one year after starting losartan treatment her Hb was 107g/l (120-150 g/l). One week later the Hb had increased to 113 g/l and two months later to 116 g/l. Losartan was withdrawn. Three months after withdrawal her Hb was 121 g/l and after eight months 122 g/l.

Sammanfattning: Anemia during losartan treatment has been reported mainly in patients undergoing hemodialysis and in renal transplanted patients. Anemia seems to be a rare adverse drug reaction and since there is no clear relationship between withdrawal of losartan and increased Hb values in the present case there might be other explanations for the anemia.

Svar: It has been shown that angiotensin II stimulates erythropoiesis in vitro and that losartan block this effect. It is speculated that this might be due to direct stimulation of AT-1 receptors present on erythroid progenitors or by effect on the erythropoietin signal transduction pathway or of the pathways of other erythroid growth factors (1). Losartan decreases hematocrits in patients with erythrocytosis after renal transplantation (2).

Two out of seventy-six renal transplanted patients, treated with losartan, developed a mild normocytic anemia and three other had an impairment of their pre-existing anemia during an efficacy and safety study of losartan treatment (3). In a cohort study there was a significantly higher risk for developing anemia during losartan treatment compared with calcium channel antagonist treatment (4).

Data regarding anemia caused or worsened by losartan during hemodialysis are contradictory.

In one retrospective study with 184 patients treatment with losartan (50 mg/day) caused decreased hemoglobin concentration and a three- to four-fold increase in the need of recombinant human erythropoietin (rHuEPO) (5). In another retrospective study, of 40 patients, comparing the need of rHuEPO in patients receiving losartan (100 mg/day) or amlodipine (10 mg/day), the mean weekly rHuEPO dose increased significantly in losartan treated patients but remained the same in amlodipine treated patients (6). In a small study where 13 patients, undergoing hemodialysis, received losartan no change in hemoglobin values was measured and rHuEPO dosage at the end of the study was similar to the dose at the beginning of treatment (7). Losartan was shown to not change the concentration of endogenous erythropoietin in patients undergoing hemodialysis in a study including 12 patients receiving losartan and 12 patients receiving captopril. In captopril treated patients there was a significant decrease in endogenous erythropoietin concentration three months after treatment initiation (8).

In the files of SADRAC (Swedish Adverse Drug Reactions Advisory Comitte) there are two cases of anemia reported. In one case the patient had had a renal transplantation (9).

In the present case there is no clear correlation between losartan and anemia since the hemoglobin level started to increase before losartan was withdrawn. In the present case there might be other reasons for the anemia. Mrug M, Stopka T, Julian B, Prchal JF, Prchal JT. Angiotensin II stimulated proliferation of normal early erythroid progenitors. J Clin Invest 1997;100:2310-4. Conlon PJ, Smith SR, Butterly DW, Brennan DC. Losartan in post-transplant erythrocytosis. Nephrol Dial Transplant 1996;11(12):2524-5. del Castillo D, Campistol JM, Guirado L, Capdevilla L, Martinez JG et al. Efficacy and safety of losartan in the treatment of hypertension in renal transplant recipients. Kidney Int Suppl 1998;68:135-9. Samizo K, Kawabe E, Hinotsu S, Sato T, Kageyama S, Hamada C et al. Comparison of losartan with ACE inhibitors and dihydropyridine calcium channel antagonists. A pilot study of prescription-event monitoring in Japan. Drug Saf 2002;25(11):811-21. Schwarzbeck A, Wittenmeier KW, Hallfritzsch U. Anaemia in dialysis patients as a side-effect of sartanes. Lancet 1998;352:286. Odabas AR, Cetinkaya R, Selcuk Y, Keles S, Bilen H. The effect of high dose losartan on erythropoietin resistance in patients undergoing haemodialysis. Panminerva Med 2003;45:59-62. Kato A, Takita T, Furuhashi M, Takahashi T, Maruyama Y, Hishida A. No effect of losartan on response to erythropoietin therapy in patients undergoing hemodialysis. Nephron 2000;86:538-9. Schiffl H, Lang SM. Angiotensin-converting enzyme inhibitors but not angiotensin II AT 1 receptor antagonists affect erythropoiesis in patients with anemia of end-stage renal disease. Nephron 1999;81:106-8. Swedis (cited 2004-01-09)