Priapism Associated with Concurrent Use of Phosphodiesterase Inhibitor Drugs and Intracavernous Injection Therapy

Case Report Priapism associated with concurrent use of phosphodiesterase inhibitor drugs and intracavernous injection therapy

CG McMahon1*

1Australian Centre for Sexual Health, Sydney, Australia

International Journal of Impotence Research (2003) 15, 383–384. doi:10.1038/sj.ijir.3901046

Keywords: erectile dysfunction; priapism; sildenafil; tadalafil; penile injections

Introduction in men following intracavernous self-administration of vasoactive drugs following administration of a phosphodiesterase inhibitor drug. The identification of the cyclic GMP/NO pathway as the final neurotransmitter messengers responsible for penile erection and the subsequent development Case 1 of highly specific phosphodiesterase enzyme inhibitors has revolutionised the treatment of erectile dysfunction. Sildenafil citrate and tadalafil citrate A 46-year-old man with type II diabetes, hyperten- are effective, well tolerated and safe treatments for sion and dyslipidaemia and a 4-year history of erectile dysfunction caused by a broad range of erectile dysfunction, presented with a painful 1,2 aetiologies. Priapism for longer than 6 h is a priapism 7 h following the administration of oral recognised complication of intracavernous injection sildenafil (100 mg) and the subsequent intracaver- therapy and have been reported to occur in 0.25% of nous administration of alprostadil (15 mg). Corporal men using alprostadil monotherapy and 0.9% of aspiration of dark deoxygenated blood confirmed men using combination pharmacotherapy contain- the presence of a low flow ischaemic priapism. The 3,4 ing alprostadil, papaverine and phentolamine. An patient had recently been prescribed sildenafil by extensive review of the published medical literature his local medical officer and had failed to achieve an and the manufacturer’s clinical trial and postmar- erection sufficient for penetration on each of the keting database identified six reports of priapism three occasions when he attempted intercourse following the use of sildenafil in an estimated 1.2 approximately 10 min after ingestion of the drug. 5–8 billion users. Several authors have reported that On the third administration, he administered an 15–25% of men previously treated with intracaver- intracavernous injection of alprostadil approxi- nous injection therapy who respond to sildenafil mately 1 h after ingestion of sildenafil. His priapism will choose to alternate between both forms of subsided after serial corporal aspiration and irriga- 9,10 therapy according to circumstance. Combination tion with dilute phenylephrine. Subsequent penile therapy using sildenafil and intracavernous combi- duplex Doppler ultrasonography did not demon- nation pharmacotherapy have been reported to strate any postpriapism corporal fibrosis. Following salvage 30% of men refractory to either treatment dose titration and re-education, he now responds 11 alone. We report three cases of priapism occurring well to sildenafil and no longer uses intracavernous injection therapy.

*Correspondence: CG McMahon, Australian Centre for Sexual Health, Hemsley House, 20 Roslyn Street, Potts Case 2 Point, Sydney NSW 2011, Australia. E-mail: [email protected] Received 19 March 2003; revised 16 May 2003; accepted 2 A 53-year-old man with a 2-year history of vasculo- June 2003 genic erectile dysfunction, initially diagnosed with Priapism associated with concurrent use of phosphodiesterase inhibitor drugs CG McMahon 384 colour duplex Doppler ultrasonography, presented co-administration of sildenafil and dihydrocodeine, with a painful 10 h priapism following the initial and suggested that acute opiate intake produced administration of sildenafil (100 mg) and the sub- abnormally high cyclic-GMP levels in peripheral sequent intracavernous administration of Trimix nerve endings and an augmented response to (0.25 ml.) A low flow ischaemic priapism was sildenafil. Yoon et al12 reported a single case confirmed by the absence of cavernous artery blood of priapism following intracavernous injection of flow on colour duplex Doppler ultrasonography and sildenafil citrate. All cases were managed conserva- the presence of deoxygenated blood on corporal tively and detumescence was achieved. aspiration. He had been treated successfully with Although the majority of patients choose mono- sildenafil since his initial presentation, but had therapy treatment with an oral PDE-5 inhibitor, a administered Trimix prescribed to his male sexual significant number of patients for reasons of perso- partner 1.5 h after administration of sildenafil to nal preference, convenience, speed of onset of augment his erection. Serial corporal aspiration and erectile response and cost, continue to use injection irrigation with dilute phenylephrine resulted in therapy intracavernous intermittently.9 It is incum- detumescence within 45 min. Subsequent penile bent on the treating physician to ensure that patients duplex Doppler ultrasonography did not demon- understand the expected duration of action of PDE-5 strate any postpriapism corporal fibrosis. inhibitors and are aware of the potential for priapism if intracavernous injection therapy is administered at either the same time or within that Case 3 period of time. This is of particular importance with tadalafil due to its relatively long half-life of 17.5 h.

A 37-year-old man with long-standing psychogenic erectile dysfunction confirmed by Rigiscan NPT References presented with a 14 h episode of priapism. He had been previously treated with psychosexual therapy and responded well with alternating use of intraca- 1 Brock GB et al. Efficacy and safety of tadalafil for the treatment vernous injection therapy using Trimix and silde- of erectile dysfunction: results of integrated analyses. J Urol nafil. He had recently been prescribed and 2002; 168: 1332. 2 Morales A et al. Clinical safety of oral sildenafil citrate responded well to tadalafil (20 mg). Approximately (VIAGRA) in the treatment of erectile dysfunction. Int J Impot 18 h after administration of tadalafil (20 mg), he Res 1998; 10: 69. administered an intracavernous injection of Trimix 3 Porst HJ. The rationale for prostaglandin E1 in erectile failure: (0.25 ml) and developed a subsequent priapism. The a survey of worldwide experience. Urology 1996; 155: 802. 4 McMahon C. A comparison of the response to the intracaver- absence of cavernous artery blood flow on colour nosal injection of a combination of papaverine and phentola- duplex Doppler ultrasonography and corporal as- mine, prostaglandin PGE1 and a combination of all three in piration of deoxygenated blood confirmed the the management of impotence. Int J Impot Res 1991; 3: 113. presence of an ischaemic priapism. He was treated 5 Sur RL Kane CJ. Sildenafil citrate-associated priapism. with serial corporal aspiration and irrigation with Urology 2000; 55: 950. 6 Aoyagi T et al. Sildenafil induced priapism. Bull Tokyo Dent dilute phenylephrine and detumesced within Coll 1999; 40: 215. 90 min. 7 Kassim AA, Fabry ME, Nagel RL. Acute priapism associated with the use of sildenafil in a patient with sickle cell trait. Blood 2000; 95: 1878. 8 Goldmeier D, Lamba H. Prolonged erections produced by Discussion dihydrocodeine and sildenafil. BMJ 2002; 324: 1555. 9 McMahon CG, Samali R, Johnson H. Efficacy, safety and patient acceptance of sildenafil citrate as a treatment for The medical literature contains six cases of silde- erectile dysfunction. J Urol 2000; 164: 1192. nafil-induced priapism. Sur and Kane5 reported a 10 Hatzichristou DG et al. Sildenafil versus intracavernous injection therapy: efficacy and preference in patients on 24-h priapism following sildenafil (100 mg) in a 28- 6 intracavernous injection for more than 1 year. J Urol 2000; year-old man and Aoyaji et al reported persistent 164: 1197. priapism in a 53-year-old man following adminis- 11 McMahon CG, Samali R, Johnson H. Treatment of intracorpor- tration of sildenafil (200 mg) 3 days earlier. Kassim eal injection nonresponse with sildenafil alone or in combina- et al7 reported a case of priapism in a 39-year-old tion with triple agent intracorporeal injection therapy. J Urol 8 1999; 162: 1992. male with sickle cell trait. Goldmeier and Lamba 12 Yoon H et al. Intracavernosal injection of sildenafil citrate: reported two cases of priapism following the misapplication of the drug. J Urol 2001; 165: 1218.

International Journal of Impotence Research