What medications are most likely to cause priapism?

From the Guidelines

Medications most likely to cause priapism include antipsychotics, antidepressants, alpha-blockers, and erectile dysfunction medications, with intracavernosal injections carrying a particularly high risk. The medications that can cause priapism are:

• Antipsychotics (particularly trazodone, chlorpromazine, thioridazine, and risperidone)
• Antidepressants (especially trazodone)
• Alpha-blockers (such as prazosin and tamsulosin)
• Erectile dysfunction medications (sildenafil, tadalafil, and vardenafil)
• Blood thinners like heparin and warfarin
• Recreational drugs like cocaine and alcohol
• Intracavernosal injections used for erectile dysfunction treatment, including papaverine, phentolamine, and alprostadil, as stated in the guideline by the American Urological Association 1. Priapism is a medical emergency requiring immediate attention if an erection lasts longer than four hours, as delayed treatment can lead to permanent erectile dysfunction due to tissue damage from prolonged oxygen deprivation, as noted in the AUA/SMSNA guideline 1. The mechanism typically involves either increased blood flow to the penis or impaired drainage, disrupting the normal balance of blood circulation. Patients taking these medications should be informed about this potential side effect and instructed to seek emergency care if priapism occurs. In patients presenting with a prolonged erection of four hours or less following intracavernosal injection pharmacotherapy for erectile dysfunction, clinicians should administer intracavernosal phenylephrine as the initial treatment option, as recommended by the AUA/SMSNA guideline 1. It is essential to differentiate between ischemic and non-ischemic priapism, as the treatment approaches differ significantly, and the diagnosis of priapism should be made promptly to initiate appropriate management, as outlined in the guideline 1. The optimal management strategy for a persistent erection following iatrogenic ICI administration is not clear, but several options are available, including oral therapies and intracavernosal phenylephrine, as discussed in the AUA/SMSNA guideline 1. Ultimately, clinical judgment is required to determine the best course of treatment for each patient, considering the underlying cause of priapism and the patient's individual needs, as emphasized in the guideline 1.

From the FDA Drug Label

Cases of priapism (painful erections greater than 6 hours in duration) have been reported in men receiving Trazodone Hydrochloride Tablets. Trazodone Hydrochloride Tablets should be used with caution in men who have conditions that might predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia), or in men with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie’s disease).

Medications likely to cause priapism:

• Trazodone Hydrochloride Tablets 2 Key factors to consider:
• Men with conditions that predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia)
• Men with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie’s disease)

From the Research

Medications Associated with Priapism

The following medications have been reported to cause priapism:

• Antipsychotics, including both typical and atypical antipsychotics 3, 4, 5, 6
• Antidepressants, particularly those with alpha-adrenergic blocking properties 4, 7
• Antihypertensives, especially those with alpha-adrenergic blocking properties 4, 7
• Recreational drugs, such as cocaine and cannabis 4, 7

Antipsychotics and Priapism

Antipsychotics are a common cause of pharmacologically-induced priapism, with approximately 50% of drug-related priapism being attributed to antipsychotic usage 5. The majority of antipsychotics have been reported to cause priapism, including:

• Typical antipsychotics, such as haloperidol and chlorpromazine 4, 6
• Atypical antipsychotics, such as olanzapine, risperidone, and clozapine 3, 4, 6
• Amisulpride is currently the only antipsychotic that does not have alpha-adrenergic affinity and is therefore preferred in cases of priapism 4

Mechanism of Priapism

The exact mechanism of priapism associated with antipsychotics is unknown, but it is thought to be related to alpha-adrenergic blockage in the corpora cavernosa of the penis 3, 4, 5, 6. This blockage inhibits detumescence, leading to a prolonged and painful erection.

Management of Priapism

The management of priapism involves immediate medical attention, with treatment options including:

• Aspiration and irrigation of the corpora cavernosa 4
• Injection of phenylephrine to reduce blood flow to the penis 7
• In select cases, early placement of a penile prosthesis may be necessary to prevent further morbidity 7