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Sexual Medicine Oct 2023Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs).
Safety profile and signal detection of phosphodiesterase type 5 inhibitors for erectile dysfunction: a Food and Drug Administration Adverse Event Reporting System analysis.
BACKGROUND
Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs).
AIM
This study aims to investigate and compare the characteristics of AEs associated with PDE5Is used for erectile dysfunction and identify any safety signals in a postmarketing surveillance database between 2010 and 2021.
METHODS
A descriptive analysis was conducted for all AEs reported to the Food and Drug Administration Adverse Event Reporting System for 4 PDE5Is-avanafil, sildenafil, tadalafil, and vardenafil-indicated for erectile dysfunction between January 2010 and December 2021. The frequency of the most reported AEs and outcomes were identified. A disproportionality analysis based on proportional reporting ratio (PRR) and reporting odds ratio (ROR) was conducted for the most common and clinically important AEs to identify signals to gain insights into potential differences in safety profiles.
OUTCOMES
The outcome measures of the study are frequency of reported AEs and outcomes following AE.
RESULTS
A total of 29 236 AEs were reported for PDE5Is during the study period. The most reported AE was "drug ineffective" with 7115 reports (24.3%). Eight safety signals were detected across the 4 drugs. Key signals were sexual disorders (PRR, 3.13 [95% CI, 2.69-3.65]; ROR, 3.24 [95% CI, 2.77-3.79]) and death (PRR, 3.17 [2.5-4.01]; ROR, 3.211 [2.52-4.06]) for sildenafil, priapism (PRR, 3.63 [2.11-6.24]; ROR, 3.64 [2.12-6.26]) for tadalafil, and drug administration error (PRR, 2.54 [1.84-3.52]; ROR, 2.6 [1.86-3.63]) for vardenafil. The most reported outcomes were other serious events with 6685 events (67.2%) and hospitalization with 1939 events (19.5%).
CLINICAL IMPLICATIONS
The commonly reported AEs and detected signals may guide clinicians in treatment decision making for men with erectile dysfunction.
STRENGTHS AND LIMITATIONS
This is the first comprehensive report and disproportionality analysis on all types of AEs associated with PDE5Is used for erectile dysfunction in the United States. The findings should be interpreted cautiously due to limitations in the Adverse Event Reporting System, which includes self-reports, duplicate and incomplete reports, and biases in reporting and selection. Therefore, establishing a causal relationship between the reported AEs and the use of PDE5Is is uncertain, and the data may be confounded by other medications and indications.
CONCLUSION
PDE5Is demonstrate significantly increased risks of reporting certain clinically important AEs. While these events are not common, it is imperative to continually monitor PDE5I use at the levels of primary care to national surveillance to ensure safe utilization.
PubMed: 38034088
DOI: 10.1093/sexmed/qfad059 -
Ultrasound Quarterly Mar 2024High-frequency ultrasound is the imaging modality of choice for evaluating penile pathology because of its easy access, low cost, and patient tolerance ( The Penis,... (Review)
Review
High-frequency ultrasound is the imaging modality of choice for evaluating penile pathology because of its easy access, low cost, and patient tolerance ( The Penis, Diagnostic Ultrasound, second edtion . Boca Raton: CRC Press; 2007:957-978). This pictorial review will illustrate the sonographic features of emergent and nonemergent penile conditions such as penile fracture, spongial tear, urethral injury, various types of priapism, erectile dysfunction, penile abscess, and Mondor disease.
Topics: Humans; Male; Erectile Dysfunction; Penile Diseases; Penis; Priapism; Ultrasonography
PubMed: 38015246
DOI: 10.1097/RUQ.0000000000000663 -
The Journal of Sexual Medicine Dec 2023Phosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism...
BACKGROUND
Phosphodiesterase type 5 (PDE5) inhibitor labeling states that these agents should not be used in conjunction with other erectogenic medications for fear of priapism occurring.
AIM
We explored the risk of priapism and prolonged erections in men in our post-radical prostatectomy (RP) penile injection program who were using regular PDE5 inhibitor and intracavernosal injections (ICIs) as part of their rehabilitation program.
METHODS
The study cohort included men on penile injection therapy who (1) were taking tadalafil 5 mg daily or taking sildenafil 25 mg on noninjection days, (2) had an RP, (3) were using their respective PDE5 inhibitor regularly at the time of penile injection training, and (4) complied with the program instructions regarding penile injection use. Demographics, comorbidity details, PDE5 inhibitor dose and utilization, and injection dose and utilization data were collected. All patients underwent in-office injection training and used trimix (papaverine/phentolamine/prostaglandin E1) as the intracavernosal medication.
OUTCOMES
Priapism was defined as a patient self-reported penetration hardness erection ≥4 hours in duration, while prolonged erection was defined as a penetration hardness erection lasting ≥2 hours.
RESULTS
A total of 112 tadalafil users and 364 sildenafil users were compared. Mean age and duration post-RP were 62 ± 14 years and 5.2 ± 12 months, respectively, and there was no difference between tadalafil and sildenafil groups. The mean trimix dose was tadalafil 24 ± 24 units and sildenafil 31 ± 37 units (P < .05). Priapism occurred in 2 (1.7%) of 112 tadalafil users and 5 (1.4%) of 364 sildenafil users (P = .47). Excluding those men experiencing priapism on any occasion, those with any reported penetration hardness erection lasting ≥2 hours were 7 (6.3%) of 112 tadalafil users and 12 (3.3%) of 364 sildenafil users (P < .01). A total of 53% of these prolonged erections occurred within the first 6 injections at home (no difference between tadalafil and sildenafil groups).
CLINICAL IMPLICATIONS
We emphasize the need for continued monitoring and education on proper injection techniques to minimize the risk of adverse events in ICI and PDE5 inhibitor combination therapy.
STRENGTHS & LIMITATIONS
This study has a relatively large patient population with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions for priapism and prolonged erections, enhances the accuracy and reliability of the results. However, there are some limitations, such as social desirability, confounding factors, and recall bias.
CONCLUSION
There is no significant difference in the incidence of priapism in an ICI program in which men combine ICI with tadalafil or sildenafil. However, tadalafil patients had a higher rate of prolonged erections, which was found to occur mostly early during the titration phase.
Topics: Male; Humans; Middle Aged; Aged; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Erectile Dysfunction; Priapism; Reproducibility of Results; Piperazines; Purines; Penile Erection; Prostatectomy
PubMed: 37973393
DOI: 10.1093/jsxmed/qdad144 -
Urology Research & Practice Nov 2023Malignant priapism (MP) is defined as a condition of persistent erection of the penis without sexual stimulation due to the neoplastic process of the cavernous sinus and...
Malignant priapism (MP) is defined as a condition of persistent erection of the penis without sexual stimulation due to the neoplastic process of the cavernous sinus and the efferent veins. The effectiveness of established therapeutic recommendations in priapism was ineffective in MP. Modalities of therapy for MP varied from medication treatment, nonsurgical treatment, surgical treatment, and radiotherapy. Despite aggressive surgical management combined with radiation therapy, chemotherapy, or targeted therapy, the survival rate remains low. Therefore, the treatment is usually palliative, focusing on the patient's quality of life improvement and symptom relief.
PubMed: 37971391
DOI: 10.5152/tud.2023.23088 -
Translational Andrology and Urology Oct 2023Malignant priapism, a rare disease with only about 500 reported cases to date, consists of persistent erection secondary to invasion or metastasis of a primary neoplasm....
BACKGROUND
Malignant priapism, a rare disease with only about 500 reported cases to date, consists of persistent erection secondary to invasion or metastasis of a primary neoplasm. While treatment guidelines for priapism in non-malignant cases have been established, there is currently no guideline for treating malignant priapism. Herein, we describe three cases of malignant priapism and suggest a step-by-step approach for clinical management.
CASE DESCRIPTION
This study reports three cases of malignant priapism resulting from advanced genitourinary cancers. All patients experienced a sub-acute progression of penile pain and ultimately underwent palliative penectomy, resulting in sustained symptom relief.
CONCLUSIONS
Treatment of malignant priapism needs to be individualized to the needs of the patient. No matter the primary or secondary nature of the disease, current data suggest that malignant priapism is associated with poor outcomes and emphasis should be put on palliative care. Similar to previous cases, our cases died shortly after the diagnosis of malignant priapism. Conventional procedures such as shunting may not necessarily provide symptom relief in these patients. Although new radiation techniques have shown favorable outcomes, penectomy should be considered the last resort in clinical management. Revisions to the existing management guidelines for priapism are necessary to address its occurrence in malignant contexts.
PubMed: 37969781
DOI: 10.21037/tau-23-327 -
Transfusion Clinique Et Biologique :... Feb 2024Hyperleukocytosis in leukemic patients may cause tumour lysis syndrome, disseminated intravascular coagulopathy, and leukostasis, resulting in decreased tissue perfusion...
Hyperleukocytosis in leukemic patients may cause tumour lysis syndrome, disseminated intravascular coagulopathy, and leukostasis, resulting in decreased tissue perfusion and increasing the risk of mortality. Since the myeloid blasts are larger than lymphoid blasts and are less deformable, complications of leukostasis are seen more frequently in myeloid leukemia. Priapism is a less common complication associated with leukostasis in leukaemia patients that should be treated as soon as possible to avoid ischemic injuries. Although chemotherapeutic drugs such as hydroxyurea and imatinib are used to treat hyperleukocytosis in CML patients, leukocytapheresis (LCP) can achieve rapid cytoreduction. Prophylactic LCP could not offer any advantage over aggressive chemotherapy, but therapeutic leukocyte depletion has a proven role in patients having symptomatic leukostasis due to high tumour burden. Three patients with ischaemic priapism were reported at our institute's emergency department, where detumescence could not be achieved by distal shunting or aspiration with phenylephrine instillation. The procedure of therapeutic LCP was performed in all three patients on an emergency basis, which resolved painful priapism by rapid cytoreduction.
Topics: Male; Humans; Priapism; Leukapheresis; Leukostasis; Tertiary Care Centers; Leukemia, Myeloid
PubMed: 37944664
DOI: 10.1016/j.tracli.2023.11.001 -
Pharmacoepidemiology and Drug Safety Jan 2024To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal...
PURPOSE
To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal drugs).
METHODS
We queried the World Health Organization global database of individual case safety reports (VigiBase) for records of the adverse drug reactions (ADR) with sildenafil, tadalafil, avanafil, vardenafil, papaverine, and alprostadil. Disproportionality analyses (case/non-case approach) were performed to assess the reporting odds ratio (ROR) of priapism reporting in PDE5i consumers compared to intracavernousal drug recipients.
RESULTS
From a total of 133 819 ADR events for erectogenic medications, 632 were priapism (PDE5is: n = 550, 0.41%; intracavernousal drugs: n = 82, 9.92%). Priapism disproportionality signals from intracavernousal drugs were 25 times stronger than PDE5is (ROR = 34.7; confidence interval [CI] 95%: 27.12-43.94 vs. ROR = 1.38; 95% CI: 1.24-1.54). For all PDE5i agents, the 12-17 years age group had the highest ROR (9.49, 95% CI: 3.76-19.93) followed by 2-11 years (4.31, 95% CI: 1.57-9.4). Disproportionality signals for consumers under 18 for both all PDE5is as a whole (ROR = 4.57, 95% CI: 2.48-7.73) and sildenafil (ROR = 4.89, 95% CI: 2.51-8.62) were stronger than individuals 18 or older (ROR = 1.06, 95% CI: 0.93-1.21 and ROR = 1.08, 95% CI: 0.91-1.26, respectively).
CONCLUSIONS
PDE5i use shows disproportionate priapism signals which are higher in young patients.
Topics: Male; Humans; Child, Preschool; Child; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Priapism; Erectile Dysfunction; Tadalafil; Drug-Related Side Effects and Adverse Reactions
PubMed: 37909414
DOI: 10.1002/pds.5721 -
International Journal of Impotence... Nov 2023Priapism is a persistent or prolonged erection, in the absence of sexual stimulation, that fails to subside. Prolonged ischaemic or low flow priapism is defined as a... (Review)
Review
Priapism is a persistent or prolonged erection, in the absence of sexual stimulation, that fails to subside. Prolonged ischaemic or low flow priapism is defined as a full or partial erection persisting for more than 4 h and unrelated to sexual interest or stimulation, characterised by little or no cavernous blood flow. Low flow priapism leads to progressive corporal fibrosis, which could, in turn, lead to long-lasting erectile dysfunction if left untreated. Penile prosthesis implantation is recognised as a management option in refractory and delayed low flow priapism for restoring erectile function with high patient satisfaction rates. However, the ensuing corporal fibrotic scarring poses a surgical challenge to clinicians, given the higher complication rates in this patient subset. Postoperative patient satisfaction has been closely linked to preoperative expectations and perceived loss of penile length. Therefore, thorough patient counselling concerning the risk and benefits of penile implants should be a priority for all clinicians. Moreover, there is a lack of consensus on the ideal prosthesis choice and procedural timing in refractory low flow priapism. In this review, we will examine the existing literature on penile implants in patients with priapism and discuss the options for managing complications associated with penile prosthesis surgery.
Topics: Male; Humans; Priapism; Penile Prosthesis; Penis; Penile Implantation; Erectile Dysfunction; Fibrosis
PubMed: 37898653
DOI: 10.1038/s41443-023-00787-1 -
Blood Advances Feb 2024Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics....
Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.3 ± 8.9 years; 389 ± 150 days after HSCT) with age-, race- and sex-matched values from healthy adults without sickle trait (n = 28; age, 30.2 ± 5.6 years). Before transplant, 7 patients had neurological indications for transplant (eg, overt stroke) and 4 had nonneurological reasons for haploidentical bone marrow transplant (haplo-BMT). All received haplo-BMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Before transplant, CBF was elevated (CBF, 69.11 ± 24.7 mL/100 g/min) compared with that of controls (P = .004). Mean CBF declined significantly after haplo-BMT (posttransplant CBF, 48.2 ± 13.9 mL/100 g/min; P = .003). OEF was not different from that of controls at baseline and did not change significantly after haplo-BMT (pretransplant, 43.1 ± 6.7%; posttransplant, 39.6 ± 7.0%; P = .34). After transplant, CBF and OEF were not significantly different from controls (CBF, 48.2 ± 13.4 mL/100 g/min; P = .78; and OEF, 39.6 ± 7.0%; P > .99). CMRO2 did not change significantly after haplo-BMT (pretransplant, 3.18 ± 0.87 mL O2/100 g/min; posttransplant, 2.95 ± 0.83; P = .56). Major complications of haplo-BMT included 1 infection-related death and 1 severe chronic graft-versus-host disease. Haplo-BMT in adults with SCD reduces CBF to that of control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls. The trial was registered at www.clinicaltrials.gov as #NCT01850108.
Topics: Adult; Child; Humans; Young Adult; Bone Marrow Transplantation; Anemia, Sickle Cell; Hematopoietic Stem Cell Transplantation; Hemodynamics; Oxygen
PubMed: 37883803
DOI: 10.1182/bloodadvances.2023010717 -
Management of Priapism: Results of a Nationwide Survey and Comparison with International Guidelines.Urology Research & Practice Jul 2023The aim of this study is to evaluate current urologic practice regarding the management of priapism in Turkey and compare with international guidelines.
OBJECTIVE
The aim of this study is to evaluate current urologic practice regarding the management of priapism in Turkey and compare with international guidelines.
METHODS
Urologists and urology residents were invited to an online survey consisting of 30 multiple-choice questions on priapism-related clinical practices that were consid- ered most important and relevant to practices by using Google Forms.
RESULTS
Total number of responses was 340. Respondents reported that they recorded a detailed patient's medical history and physical examination findings (n = 340, 100%) and laboratory testing, which includes corporal blood gas analysis (n=323, 95%). Participants announced that they performed Doppler ultrasound for 1/4 cases (n = 106, 31%), but 22% of the participants (n=75) replied that they performed in >75% of cases. Participants (n=311, 91%) responded that the first-line treatment of ischemic priapism is decompression of the corpus cavernosum. Moreover, most respondents (n = 320, 94%) stated that sympathomimetic injection drugs should be applied as the second step. About three-quarters of respondents (n = 247, 73%) indicated adrenaline as their drug of choice. Phosphodiesterase type 5 inhibitors seems to be the most pre- ferred drug for stuttering priapism (n=141, 41%). Participants (n=284, 84%) replied that corpora-glanular shunts should be preferred as the first. A large number of par- ticipants (n = 239, 70%) declared that magnetic resonance imaging can be performed in cases with delayed (>24 hours) priapism to diagnose corporal necrosis. Most of the participants (84%) responded that penile prosthesis should be preferred to shunts in cases with delayed (>48 hours) priapism.
CONCLUSION
It would be appropriate to improve the training offered by professional associations and to give more training time to the management of priapism during residency.
PubMed: 37877823
DOI: 10.5152/tud.2023.22209