Is there any documentation to support the statement that ranitidine is less likely to exert an anti

Fråga: Is there any documentation to support the statement that ranitidine is less likely to exert an antiandrogenic effect than cimetidine?

Sammanfattning: Reports in the literature show that anti-androgenic side effects are a potential problem with both cimetidine and ranitidine. There is some experimental evidence suggesting that ranitidine may have less anti-androgenic effect than cimetidine, but the clinical importance of this has not been demonstrated. At the present time recommendations on the selection of one H2-antagonist over another should not be made on their likelyhood of producing these side effects as they are quite rare and no difference in incidence has been shown. However, if these effects manifest during cimetidine treatment, particularly if it is prolonged and at high dose, changing to an equipotent dose of ranitidine may allow continued H2-antagonist treatment with amelioration of anti-androgenic effects.

Svar: In controlled therapeutic trials comparing ranitidine with cimetidine, side effects have been infrequent with both drugs. The reported incidence is about 5 per cent with ranitidine and 4 per cent with cimetidine (1). Isolated case reports of anti-androgenic side effects (breast tenderness, gynecomastia, decreased libido, impotence) have been reported for both drugs (1-4). These symptoms appear to be reversible and may subside during continued therapy.

Experimental data have shown both drugs to have endocrinologic effects. Animal studies using radioligand binding have shown interference with the binding of dihydrotestoserone to androgen receptor sites for cimetidine but not ranitidine (5). In possible concurrence with these results, some investigators have reported increased plasma testosterone during treatment with cimetidine (6) but not ranitidine (6,7).

Hyperprolactinemia, which has been associated with sexual dysfunction in males, has been demonstrated in individuals administered both cimetidine (2) and ranitidine (8). No cause and effect relationship between any of these findings and anti-androgenic effects has been established.

Case reports have shown that gynecomastia and sexual impotence after prolonged treatment with cimetidine, especially at the high doses needed to control Zollinger-Ellison syndrome, have resolved after switching to ranitidine (9). 1 Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS: Ranitidine: a review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases. Drugs 1982; 24: 267-303 2 Peden NR, Cargill JM, Browning MCK, Saunders JHB, Wormsley KG: Male sexual dysfunction during treatment with cimetidine. Br Med J 1979; I: 659 3 Gough K: Different doses of ranitidine in long-term treatment of duodenal ulcer: interim analysis. In: The clinical use of ranitidine. (eds): Misiewicz JJ, Wormsley KG. Medicine Publishing Foundation, Symposium Series 5. Medicine Publishing Foundation, Oxford 1982, s. 196-200 4 Quina M: Clinical trial of ranitidine in duodenal ulcer in Portugal. In: The clinical use of ranitidine. (eds): Misiewicz JJ, Wormsley KG. medicine Publishing Foundation, Symposium Series 5. Medicine Publishing Foundation, Oxford 1982, s. 178-179 5 Pearce P, Funder JW: Histamine H2 receptor antagonist: radioreceptor assay for antiandrogenic side effects. Clin Exp Pharmacol Physiol 1980; 7: 442 6 Peden NR, Boyd EJS, Browning MC, Saunders JHB, Wormsley KG: Effects of two histamine H2-receptor blocking drugs on basal levels of gonadotropins, prolactin, testosterone and oestradiol-17beta during treatment of duodenal ulcer in male patients. Acta Endocrinol (Kbl) 1981; 96: 564-568 8 Bohnet HG, Riley AJ: An investigation of the effect of oral ranitidine treatment on hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal function in male and female volunteers. In: The clinial use of ranitidine. (eds): Misiewicz JJ, Wormsley KG. Medicine Publishing Foundation, Symposium Series 5. Medicine Publishing Foundation, Oxford 1982, p. 70-77 8 Meyler/Herxheimer, Side effects of drugs, 1983; Annual 7: 182-188 9 Jaek D, Richards DA, Granata F: Side-effects of ranitidine. Lancet 1982; II: 264-265