What is the risk of priapism when taking standard doses of Tadalafil (Phosphodiesterase type 5 (PDE5) inhibitor) or Sildenafil (PDE5 inhibitor)?

From the Guidelines

Priapism is a rare but serious side effect of PDE5 inhibitors like Tadalafil and Sildenafil, with the risk being less than 1% when taken at standard doses. For Tadalafil, the standard dose ranges from 2.5-20mg, while Sildenafil is typically prescribed at 25-100mg. Patients should be aware that priapism is defined as an erection lasting more than 4 hours and requires immediate medical attention as it can cause permanent tissue damage.

Key Points to Consider

• Risk factors that increase the likelihood of priapism include sickle cell disease, leukemia, multiple myeloma, cocaine or alcohol use, and concurrent medications like antidepressants or antipsychotics.
• The mechanism behind PDE5 inhibitor-induced priapism involves prolonged smooth muscle relaxation in the penis due to sustained inhibition of the enzyme that breaks down cGMP, leading to persistent vasodilation.
• If an erection lasts longer than 4 hours, patients should seek emergency care immediately, as treatment delay can result in permanent erectile dysfunction.

Evidence-Based Recommendations

According to the American College of Physicians guideline 1, the risk of priapism with PDE5 inhibitors is less than 1%, and trials evaluated for this guideline did not report priapism. Prolonged erection and priapism were reported infrequently during postmarketing surveillance 1.

Important Considerations for Clinicians

When prescribing PDE5 inhibitors, clinicians should consider the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile 1. The evidence is insufficient to compare the efficacy and adverse effects of different PDE-5 inhibitors for the treatment of ED because only few head-to-head trials are available 1.

Final Thoughts

In conclusion, while priapism is a rare but serious side effect of PDE5 inhibitors, the risk can be minimized by proper patient selection, education, and monitoring. Clinicians should be aware of the risk factors and mechanisms behind PDE5 inhibitor-induced priapism and take steps to mitigate them. By following evidence-based guidelines and recommendations, clinicians can provide effective and safe treatment for patients with erectile dysfunction.

From the FDA Drug Label

There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention Tadalafil should be used with caution in patients who have conditions that might predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease). Use sildenafil citrate with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease) or in patients who have conditions, which may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia). In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism (painful erection greater than 6 hours in duration) is not treated immediately, penile tissue damage and permanent loss of potency could result.

The risk of priapism when taking standard doses of Tadalafil or Sildenafil is considered rare. However, patients with certain conditions, such as:

• Sickle cell anemia
• Multiple myeloma
• Leukemia
• Anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease) may be more predisposed to priapism. It is essential for these patients to seek immediate medical attention if they experience an erection lasting greater than 4 hours. Priapism can result in irreversible damage to the erectile tissue if not treated promptly 2 3.

From the Research

Risk of Priapism with Tadalafil or Sildenafil

The risk of priapism when taking standard doses of Tadalafil or Sildenafil is relatively low.

• A study published in 2023 4 found that priapism occurred in 2 (1.7%) of 112 tadalafil users and 5 (1.4%) of 364 sildenafil users.
• The same study found that prolonged erections (defined as a penetration hardness erection lasting ≥2 hours) occurred in 7 (6.3%) of 112 tadalafil users and 12 (3.3%) of 364 sildenafil users.
• Another study published in 2005 5 reported a case of tadalafil-associated priapism in a healthy 46-year-old man.
• There have been reports of sildenafil-induced priapism, including a case reported in 1999 6 and another in 2000 7.
• A study published in 2009 8 found no increase in adverse events, including priapism, with a higher dose of sildenafil (100 mg) compared to a lower dose (50 mg).

Comparison of Tadalafil and Sildenafil

• The 2023 study 4 found no significant difference in the incidence of priapism between tadalafil and sildenafil users.
• However, the study found that tadalafil users had a higher rate of prolonged erections, which occurred mostly during the early titration phase.
• The study suggests that the risk of priapism and prolonged erections can be minimized with proper education and monitoring of patients using these medications.