Drugs for erectile dysfunction in patients with cerebral aneurysms?

Fråga: Is there any documentation on the use of drugs for erectile dysfunction in patients with cerebral aneurysms?

Sammanfattning: A number of cases have been reported on intracranial hemorrhages during the use of PDE5 inhibitors. It does however seem to be a rare side effect. Less information can be identified on hemorrhage with the use of alprostadil and no case reports have been found in PubMed. The risk with the use of this drug is therefore even more difficult to assess. Aneurysms in combination with sexual activity are risk factors for hemorrhage. Intracranial hemorrhages are rare when using drugs for erectile dysfunction but an increased risk could result from the combination with other risk factors. We recommend a discussion of the risk in this case with a neurosurgeon.

Svar: Stroke, both ischemic and hemorrhagic, is listed as a rare side effect to treatment with sildenafil/tadalafil (>1/10 000 to <1/1 000). According to the product resume of tadalafil most of these patients had cardiovascular risk factors. The use of sildenafil/tadalafil is a contraindicated in patients who recently had a stroke, in the case of tadalafil this is specified as the first 6 months (1,2). Alprostadil has instable cardiovascular or cerebrovascular conditions as a contraindication in the product resumé for Vitaros. No clear signs exists that there is an increased risk of cardiovascular events other than the vasodilating effects from alprostadil. It cannot however be ruled out that patients with underlying risk factors has an increased risk in combination with increased sexual or physical activity and the use of alprostadil according to the producer (3).

There have been earlier questions to the drug information center on sildenafil/tadalafil and the risk of intracranial hemorrhage and a number of case reports were found at those times. One describes a 70-year-old man who had an intracerebral hemorrhage with a debut of symptoms one hour after having taken 40 mg of tadalafil. The symptoms got slightly worse during intercourse (4). In this case the dose was the double recommended dose (1). Another case report describes a probable overdose of sildenafil followed by sexual intercourse after which intracerebral hemorrhage resulting in death of the patient ensued. A third case report describes an intracerebral hemorrhage following the intake of two pills of 25 mg sildenafil within an hour and without intercourse. There are reports on cerebral ischemia as well after intake of sildenafil. Other reports describe other forms of hemorrhage such as epistaxis and bleeding hemorrhoids while using sildenafil. It has been suggested that sildenafil through vasodilation might trigger hemorrhage in susceptible patients. Ex vivo studies has shown that sildenafil can reduce the PDE5 induced platelet aggregation. A dose of 100 mg has been shown to increase the bleeding time significantly whereas 50 mg did not (5).

Since these earlier questions to the drug information center, a further number of case reports have been published that describe intracerebral and subarachnoidal hemorrhages after intake of sildenafil or tadalafil (6-12). In one of those cases a man who died from a subarachnoid hemorrhage due to rupture of an aneurysm on the anterior cerebral artery is described. The patient had intercourse after taking sildenafil (7). In another case report a man is described whom, after intake of vardenafil 30 mg and intercourse, had an intracerebral hemorrhage (13). No reports on intracranial hemorrhages during the use of alprostadil can be found when searching PubMed.

The Swedish database on adverse drug effects contains 3 reports on hemorrhage during the use of drugs for erectile dysfunction. One case concerns intracerebral hemorrhage with the use of sildenafil during sexual intercourse. An aneurysm was found in the patient; however, it is not clearly stated in the report that the aneurysm was the cause of the hemorrhage. There is a report describing subdural hemorrhage after using sildenafil in a patient who was using warfarin as well. Another report describes a man who died due to a ruptured aortic aneurysm when using Revatio (sildenafil) and warfarin. Furthermore one report describes epistaxis during use of a drug for erectile dysfunction (14). Fass. Cialis (tadalafil). Lilly (2014-02-14)

Fass. Viagra (sildenafil). Pfizer (2014-03-20)
Fass. Vitaros (alprostadil). Sandoz (2014-03-06)
Drugline no 23741 (2008-10-14)
Drugline no 20307 (2003-09-29)

Ayberk G, Ozveren MF, Yaman ME, Tosun H. Intracerebral hemorrhage after sildenafil citrate use: an incidental association? Urol J 2014 May 7;11(2):1524-6 De-Giorgio F, Arena V, Arena E, Lodise M, Valerio L, dAloja E, Chiarotti M. Subarachnoid hemorrhage during sexual activity after sildenafil intake: an accidental association? Am J Forensic Med Pathol 2011 Dec;32(4):310-1 Sheikh-Taha M, Alaywa RA. Subarachnoid hemorrhage associated with tadalafil. Am J Health Syst Pharm 2011 Jul 1;68(13):1195-6 Byoun HS, Lee YJ, Yi HJ. Subarachnoid hemorrhage and intracerebral hematoma due to sildenafil ingestion in a young adult. J Korean Neurosurg Soc 2010 Mar;47(3):210-2 Kaneria MV, Pagar S, Samant H, Yeole S, Patil S. Subarachnoid haemorrhage: possibly caused by the illegitimate use of sildenafil citrate. J Assoc Physicians India 2008 Oct;56:809-11 Alpsan MH, Bebek N. Ciftci FD, Coban O, Bahar S, Tuncay R: Intracerebral hemorrhage associated with sildenafil use: a case report. J Neurol 2008 Jun;255(6):932-3 Gazzeri R, Neroni M, Galarza M, Esposito S. Intracerebral hemorrhage associated with ue of tadalafil (Cialis). Neurology 2008 Apr 8;70(15):1289-90 McGee HT, Egan RA, Clark WM. Visual field defect and intracerebral hemorrhage associated with use of vardenafil (Levitra). Neurology 2005 Mar22;64(6):1095-6 Swedis. Svenska Biverkningsdatabasen. Rapporter inkomna mellan år 1983 och 2013 för gruppen potensmedel.