Does treatment with isotretinoin increase the risk of venous thromboembolism?/nBecause of its stron

Fråga: Does treatment with isotretinoin increase the risk of venous thromboembolism?

Because of its strong teratogenic properties, isotretinoin is always prescribed in combination with oral contraceptives to young women. Could isotretinoin in any way influence the risk of venous thromboembolism in these women?

Sammanfattning: We have found no indications in the literature that isotretinoin should increase the risk of venous thromboembolism. If isotretinoin has any effect on coagulation it seems rather to be the opposite.

Svar: A thorough literature search, including Medline, Embase and the files of the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) has been performed. In summary, we have found no indications that isotretinoin should cause venous thrombosis. Out of a total of 94 SADRAC reports of side effects connected to isotretinoin, only two refer to the circulatory system. There is one case of thrombophlebitis in a 29-year-old woman, but the relation to the isotretinoin treatment is rather weak. (She was treated without complications throughout a year. The symptoms developed after three months in a second period of treatment).

No case reports concerning thrombosis and isotretinoin or interactions between oral contraceptives and isotretinoin have been found in Medline or Embase. Nor has the manufacturer received any such reports (1).

On the contrary, some indications have been found in the literature that retinoids may enhance plasma fibrinolytic activity by way of stimulating the production of tissue-type plasminogen activator (t-PA), as shown in animal studies and in vitro cultured cells (2-4).

The effect of isotretinoin on coagulation is also discussed in an earlier Drugline document, stating that there are some reports in the literature concerning increased bleeding tendency in connection with isotretinoin treatment (5). 1 Personal communication Birgitta Börjesson, Roche 2 Declerck PJ, Boden G, Degreef H, Collen D: Influence of oral intake of retinoids on the human plasma fibrinolytic system. Fibrinolysis 1993; 7: 347-351 (Embase, abstract) (enclosed) 3 Bulens F, Nelles L, Van den Panhuyzen N, Collen D: Stimulation by retinoids of tissue-type plasminogen activator secretation in cultured human endothelial cells: Relations of structure to effect. J Cardiovasc Pharmacol 1992; 19: 508-514 (Embase, abstract) 4 Kooistra T, Opdenberg JP, Toet K, Hendriks HFJ, Van den Hoogen RM, Emeis JJ: Stimulation of tissue-type plasminogen activator synthesis by retinoids in cultured human endothelial cells and rat tissues in vivo. Thromb Haemostasis 1991; 65: 565-572 (Embase, abstract) 5 Drugline nr 11483 (year 1995) (enclosed)