Brief Report Deep Venous Thrombosis and Venous Thrombophlebitis Associated with Alprostadil Treatment for Erectile Dysfunction

Brief Report Deep venous thrombosis and venous thrombophlebitis associated with alprostadil treatment for erectile dysfunction

L Barthelmes1*, C Chezhian1 and EK Aihaku1

1Department of Urology, Ysbyty Gwynedd, Bangor, Gwynedd, UK

We report a patient who developed deep vein thrombosis of the calf and thrombophlebitis after treatment with intracorporeal alprostadil (Viridal1). The reaction recurred on rechallenge with Viridal1. 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

Keywords: erectile dysfunction; alprostadil; deep venous thrombosis; thrombophlebitis

Case report Discussion

A 63-y-old man attended the erectile dysfunction Intracavernosal injections for the treatment of clinic. He was initially treated with intracavernosal erectile dysfunction have been practiced over the injection of 20 mg alprostadil (Viridal1). Due to the last 20 y. Common complications include localised poor response he used intraurethral alprostadil fibrotic changes of the corpora cavernosa, priapism, (MUSE1), 1000 mg, without any effect. He reatten- needle breakage, haematoma and infection.1–4 ded the clinic and injected himself with a higher Alprostadil is synthetic prostaglandin E1. It acts dose of alprostadil — 40 mg — under medical super- by relaxing cavernosal smooth muscle, thereby vision. It did not result in an erection in the clinic. increasing penile blood flow, which in turn com- On his way home he noted his left calf to be swollen, presses venous outflow allowing an erection to warm and tender. This reaction subsided over the occur. course of the following 3 days when the patient The British National Formulary quotes swelling readministered the drug himself. Swelling and of leg veins as one of the side effects.5 At the time of tenderness of the left calf flared up again. The writing, the Committee on Safety of Medicines injection did not result in an erection and the (CSM)=Medicines Control Agency have received patient stopped this form of treatment. seven reports (see Table 1) of leg swelling, venous On examination at the follow-up clinic 3 months thrombosis and venous thrombophlebitis which later the left calf was swollen measuring 42.3 cm as were suspected to be associated with alprostadil opposed to 39.3 cm on the right 23 cm above the (CSM, personal communication). Even though in- medial malleolus. Small distended superficial veins formation regarding these adverse reactions is were noted over the shin on the left, which were not limited it seems that certain patients are prone to present on the right and the diagnosis of deep calf develop venous thrombosis and thrombophlebitis vein thrombosis was made on clinical grounds. The after administration of alprostadil. Phlebitis at the patient’s past medical history is uneventful. There is site of venepuncture in patients who receive no history of a previous deep venous thrombosis or prostanglandin infusion therapy for peripheral trauma of that leg. He is on no other medication. 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. *Correspondence: L Barthelmes, 4 Blaen y Wawr, Bangor LL57 4TR, UK. In conclusion, we recommend taking a detailed E-mail: [email protected] history of venous thrombosis and thrombophlebitis Received 3 January 2002; accepted 16 January 2002 before starting treatment of alprostadil for erectile Brief Report L Barthelmes et al 200 Table 1 Suspected cases of deep venous thrombosis and thrombophlebitis associated with alprostadil treatmenta

Patient Age (years) Drug Dose Reaction Details Risk factors Medication

1 58 Caverject Deep venous thrombosis 2 52 Caverject Deep venous thrombosis 3 56 MUSE 1000 mg Deep venous thrombosis Thrombus extended to Diabetes mellitus Aspirin external iliac vein and inferior vena cava Indapamide Enalapril Verapamil Humulin 4 56 MUSE 250 mg Thrombophlebitis 5 74 MUSE 1000 mg Thrombophlebitis Deep venous thrombosis 6 73 MUSE Deep venous thrombosis Reaction occurred after Aspirin 1 y of MUSE therapy Diltiazem Nizatidine Isosorbide mononitrate 7 (Case report) 63 Viridal 40 mg Deep venous thrombosis Reaction occurred within 1 h of application and on re-challenge

aReproduced with kind permission of the Medicines Control Agency.

dysfunction. In view of the limited data the history 2 Jeunemann K-P, Manning M, Krauntschick A, Alken P. 15 years of deep venous thrombosis or thrombophlebitis may of injection therapy in erectile dysfunction — a review. Int J Impot Res 1996; 8: 14. not be a formal contraindication to treatment with 3 Beer SJ, See WA. Intracorporeal needle breakage: an unusual alprostadil, but the patient should be made aware of complication of papaverine injection therapy for impotence. this possible complication to decide whether he is J Urol 1992; 147: 148 – 150. prepared to take the risk of this form of treatment. 4 Schwarzer JU, Hofmann R. Purulent corporeal cavernositis secondary to papaverine-induced priapism. J Urol 1991; 146: 845 – 846. 5 British National Formulary. September 2001; 41: 399. References 6 Fujita M et al. Neutralization of prostaglandin E1 intravenous solution reduces infusion phlebitis. Angiology 2000; 51: 719 – 723. 1 Lakin MM et al. Intracavernous injection therapy: analysis of results and complications. J Urol 1990; 143: 1138 – 1141.

International Journal of Impotence Research