Department of Urology, Ysbyty Gwynedd, Bangor, Gwynedd, UK

Correspondence to: L Barthelmes, 4 Blaen y Wawr, Bangor LL57 4TR, UK. E-mail: barthelmes@tinyonline.co.uk

We report a patient who developed deep vein thrombosis of the calf and thrombophlebitis after treatment with intracorporeal alprostadil (ViridalÒ). The reaction recurred on rechallenge with ViridalÒ. This adverse effect has not been reported in the literature but six patients have been reported to the Medicines Control Agency in Great Britain. The history of deep venous thrombosis or thrombophlebitis may not be a formal contraindication to treatment with alprostadil, but the patient should be made aware of this possible complication before embarking on this form of treatment.

International Journal of Impotence Research (2002) 14, 199-200. doi:10.1038/sj.ijir.3900853

erectile dysfunction; alprostadil; deep venous thrombosis; thrombophlebitis

Case report

A 63-y-old man attended the erectile dysfunction clinic. He was initially treated with intracavernosal injection of 20 g alprostadil (ViridalÒ). Due to the poor response he used intraurethral alprostadil (MUSEÒ), 1000 g, without any effect. He reatten-ded the clinic and injected himself with a higher dose of alprostadil¾40 g¾under medical supervision. It did not result in an erection in the clinic. On his way home he noted his left calf to be swollen, warm and tender. This reaction subsided over the course of the following 3 days when the patient readministered the drug himself. Swelling and tenderness of the left calf flared up again. The injection did not result in an erection and the patient stopped this form of treatment.

On examination at the follow-up clinic 3 months later the left calf was swollen measuring 42.3 cm as opposed to 39.3 cm on the right 23 cm above the medial malleolus. Small distended superficial veins were noted over the shin on the left, which were not present on the right and the diagnosis of deep calf vein thrombosis was made on clinical grounds. The patient's past medical history is uneventful. There is no history of a previous deep venous thrombosis or trauma of that leg. He is on no other medication.

Discussion

Intracavernosal injections for the treatment of erectile dysfunction have been practiced over the last 20 y. Common complications include localised fibrotic changes of the corpora cavernosa, priapism, needle breakage, haematoma and infection.^1,2,3,4

Alprostadil is synthetic prostaglandin E1. It acts by relaxing cavernosal smooth muscle, thereby increasing penile blood flow, which in turn compresses venous outflow allowing an erection to occur.

The British National Formulary quotes swelling of leg veins as one of the side effects.⁵ At the time of writing, the Committee on Safety of Medicines (CSM)/Medicines Control Agency have received seven reports (see Table 1) of leg swelling, venous thrombosis and venous thrombophlebitis which were suspected to be associated with alprostadil (CSM, personal communication). Even though information regarding these adverse reactions is limited it seems that certain patients are prone to develop venous thrombosis and thrombophlebitis after administration of alprostadil. Phlebitis at the site of venepuncture in patients who receive prostanglandin infusion therapy for peripheral vascular disease is recognized.⁶ Thrombophlebitis and venous thrombosis occurring distant to the site of injection has not been described previously. The mechanism remains unclear.

In conclusion, we recommend taking a detailed history of venous thrombosis and thrombophlebitis before starting treatment of alprostadil for erectile dysfunction. In view of the limited data the history of deep venous thrombosis or thrombophlebitis may not be a formal contraindication to treatment with alprostadil, but the patient should be made aware of this possible complication to decide whether he is prepared to take the risk of this form of treatment.

1 Lakin MM et al. Intracavernous injection therapy: analysis of results and complications. J Urol 1990; 143: 1138-1141. MEDLINE

2 Jeunemann K-P, Manning M, Krauntschick A, Alken P. 15 years of injection therapy in erectile dysfunction¾a review. Int J Impot Res 1996; 8: 14.

3 Beer SJ, See WA. Intracorporeal needle breakage: an unusual complication of papaverine injection therapy for impotence. J Urol 1992; 147: 148-150. MEDLINE

4 Schwarzer JU, Hofmann R. Purulent corporeal cavernositis secondary to papaverine-induced priapism. J Urol 1991; 146: 845-846. MEDLINE

5 British National Formulary. September 2001; 41: 399.

6 Fujita M et al. Neutralization of prostaglandin E1 intravenous solution reduces infusion phlebitis. Angiology 2000; 51: 719-723. MEDLINE

Table 1 Suspected cases of deep venous thrombosis and thrombophlebitis associated with alprostadil treatment^a