Can alprostadil (Caverject) cause a cerebral hemorrhage?/nBackground: A 64-year-old man with erecti

Fråga: Can alprostadil (Caverject) cause a cerebral hemorrhage?

Background: A 64-year-old man with erectile dysfunction is currently taking alprostadil (Caverject) 20 micrograms/injection. His wife notes that he had trouble with the injection process. After an injection on 8/1 he feels coldness in his legs, and cramps in his right leg. On 9/1 he began to talk irregularly, and walked into doors. On presentation to the emergency room, he is noted to have a decreased vision field, aphasia, ataxia, and borderline hypertonia. After admission, a CT-scan revealed a parietal bleeding of 20 mls, and an EKG showed the patient to be in atrial fibrillation, which resolved by the next day.

Sammanfattning: Due to the fact that alprostadil will reach the systemic circulation after local injection into the penis and the drug is known to interfere with blood pressure regulation in rare cases, a causal relationship may be indirect with the cerebral hemorrhage and cannot be excluded in this patient.

Svar: Alprostadil is a synthetic form of prostaglandin E1. Prostaglandin E1 has several physiological effects such as: vasodilation, smooth muscle relaxation, and inhibition of platelet aggregation (1). After intercavernous injection, alprostadil is either locally metabolized, or cleared into the systemic circulation. From there it undergoes extensive (67.8 to 89.1 per cent) metabolism in the lungs through a first pass mechanism (2). Its uses include erectile dysfunction (Caverject) and the management of patent ductus arteriosus (intravenous formulation only) (3).

Known side effects of Caverject are: penile pain, hematoma, priapism, hypotension, postural hypotension, fibrosis, ecchymosis, erythema, testicular pain, and abdominal wall pain (3). Other side effects noted in the literature are: syncope, penile burning sensation, penile curvature (2), palpable penile nodules, and painful erections (4).

Lea et al cite a report which says that the alprostadil from the Carvoject injections reaches the systemic circulation, so proper dosing should be exercised (2). Postural hypotension and blood pressure changes are listed as rare side effects of local administration of alprostadil (3).

Side effects seen with the intravenous formulation include: flushing, hypotension, dysrhythmias (supraventricular, ventricular, junctional, or a combination), increased heart rate (5), necrotizing enterocolitis, apnea, bradycardia, convulsions, arterial hemorrhage (6), cerebral bleeding, heart block, and ventricular fibrillation (7). Arterial hemorrhage was seen at doses of as little as 0.005-0.01 mcg/kg/min (6). An 80 kg patient could have received 0.25 mcg/kg/injection. 1 Dollery, Therapeutic drugs. 1991; 1st ed: A53- 2 Lea AP, Bryson HM, Balfour JA: Intracavernous alprostadil. Drugs Aging 1996; 8: 56-74 3 Fass 1997 (Swedish Catalogue of Approved Medical Products) 4 Canale D, Lencioni GR, Morelli G, Gasperi M, Macchia E: Long-term intracavernous self-injection with prostaglandin E1 for the treatment of erectile dysfunction. Int J Androl 1996; 19: 28-32 5 Bone RC, Slotman G, Maunder R, Silverman H, Hyers TM, Kerstein MD, Ursprung JJ: Randomized double-blind multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Chest 1989; 96: 114-119 6 Singh GK, Fong LV, Salmon AP, Keeton BR: Study of low dosage prostaglandin - usages and complications. Eur Heart J 1994; 15: 377-381 7 Physician´s Desk Reference