PMID- 33483603 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20230129 IS - 1476-5489 (Electronic) IS - 0955-9930 (Linking) VI - 34 IP - 2 DP - 2022 Mar TI - Combination therapy with topical alprostadil and phosphodiesterase-5 inhibitors after failure of oral therapy in patients with erectile dysfunction: a prospective, two-arm, open-label, non-randomized study. PG - 164-171 LID - 10.1038/s41443-020-00400-9 [doi] AB - Phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line therapeutic option for erectile dysfunction (ED), while second-line therapy includes the alprostadil. Due to the different pharmacodynamic mechanism of PDE5Is and alprostadil, a synergistic action is conceivable when they are administered in combination. The aim of present study was to evaluate the efficacy and safety of combination therapy with PDE5I and topical alprostadil in patients with ED non-responders to PDE5I alone. We designed a prospective, two-arm, open-label, non-randomized study. Patients over 18 years old, with a stable sexual relationship for at least 6 months, and ED non-responders to PDE5I monotherapy were included in the study. At baseline the variables assessed were 5-item version of the International Index of Erectile Function (IIEF-5), and Sexual Encounter Profile Questions 2 and 3 (SEP-2 and SEP-3). In addition, all subjects underwent penile dynamic duplex ultrasonography. All patients were assigned to the monotherapy group (Group A) or combination therapy group (Group B) based on their preference. Topical alprostadil 300 mug/100 mg (Virirec(R)) was the treatment assigned to Group A, while the combination therapy with the last PDE5I taken (at the maximum recommended dose) plus topical alprostadil 300 mug/100 mg (Virirec(R)) was assigned to Group B. After 3 months from assignment to groups were evaluated IIEF-5, SEP-2 and SEP-3 regarding the last sexual intercourse, and Global Assessment Questionnaire-Questions 1 and 2 (GAQ-1 and GAQ-2). All adverse events (AEs) that occurred during the study period were recorded. A total of 170 patients were included in the study (72 in Group A and 98 in Group B). Fifty-two patients were previously treated with sildenafil 100 mg (30.6%), 6 with vardenafil 20 mg (3.5%), 56 with tadalafil 20 mg (32.9%), and 56 with avanafil 200 mg (32.9%). No significant differences among the study groups were found at baseline (p > 0.05). The mean IIEF-5 score increased significantly in Group B after treatment compared to baseline (12.4 +/- 3.4 vs. 17.1 +/- 4.5; p < 0.001), conversely patients in Group A showed no significant increase (12.2 +/- 2.5 vs. 12.7 +/- 3.1; p = 0.148). The number of affirmative responses to SEP-2 was significantly higher after treatment compared to baseline only in Group B (57 vs. 78; p < 0.001). The number of affirmative responses to SEP-3 was significantly higher after treatment compared to baseline in both groups (p < 0.001). The number of affirmative responses to GAQ-Q1 and GAQ-Q2 was significantly higher in Group B compared to Group A (p < 0.001). A total of 59 (34.7%) patients experienced AEs. They were mild, self-limited, and did not cause discontinuation of treatment. No episode of priapism was recorded. No statistically significant difference was recorded between the AEs of the two groups, except for facial flushing that was reported only in Group B (p = 0.021). The combination therapy with topical alprostadil and PDE5I seems to be more effective than topical alprostadil alone without worsening the safety of the treatment. CI - (c) 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature. FAU - Garrido-Abad, Pablo AU - Garrido-Abad P AUID- ORCID: 0000-0003-2734-9387 AD - Urology Department, Hospital Universitario del Henares, Universidad Francisco de Vitoria, Coslada, Madrid, Spain. pgabad@hotmail.com. AD - Lyx Institute of Urology, Universidad Francisco de Vitoria, Madrid, Spain. pgabad@hotmail.com. FAU - Senra-Bravo, Isabel AU - Senra-Bravo I AD - Urology Department, Hospital Universitario del Henares, Universidad Francisco de Vitoria, Coslada, Madrid, Spain. FAU - Manfredi, Celeste AU - Manfredi C AUID- ORCID: 0000-0002-9706-8516 AD - Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Fernandez-Pascual, Esau AU - Fernandez-Pascual E AUID- ORCID: 0000-0002-2602-2617 AD - Lyx Institute of Urology, Universidad Francisco de Vitoria, Madrid, Spain. FAU - Linares-Espinos, Estefania AU - Linares-Espinos E AD - Lyx Institute of Urology, Universidad Francisco de Vitoria, Madrid, Spain. FAU - Fernandez-Arjona, Manuel AU - Fernandez-Arjona M AD - Urology Department, Hospital Universitario del Henares, Universidad Francisco de Vitoria, Coslada, Madrid, Spain. FAU - Varillas-Delgado, David AU - Varillas-Delgado D AD - Unidad de Apoyo a la Investigacion, Facultad de Medicina, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcon, Madrid, Spain. FAU - Martinez-Salamanca, Juan Ignacio AU - Martinez-Salamanca JI AD - Lyx Institute of Urology, Universidad Francisco de Vitoria, Madrid, Spain. LA - eng PT - Clinical Study PT - Journal Article DEP - 20210122 PL - England TA - Int J Impot Res JT - International journal of impotence research JID - 9007383 RN - 0 (Phosphodiesterase 5 Inhibitors) RN - F5TD010360 (Alprostadil) SB - IM CIN - J Urol. 2022 Oct;208(4):917-919. PMID: 35881852 MH - Administration, Topical MH - Adult MH - *Alprostadil/administration & dosage MH - Double-Blind Method MH - Drug Therapy, Combination/adverse effects MH - *Erectile Dysfunction/drug therapy MH - Humans MH - Male MH - *Phosphodiesterase 5 Inhibitors/administration & dosage MH - Prospective Studies MH - Treatment Failure EDAT- 2021/01/24 06:00 MHDA- 2022/04/01 06:00 CRDT- 2021/01/23 05:37 PHST- 2020/06/05 00:00 [received] PHST- 2020/12/04 00:00 [accepted] PHST- 2020/12/03 00:00 [revised] PHST- 2021/01/24 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/01/23 05:37 [entrez] AID - 10.1038/s41443-020-00400-9 [pii] AID - 10.1038/s41443-020-00400-9 [doi] PST - ppublish SO - Int J Impot Res. 2022 Mar;34(2):164-171. doi: 10.1038/s41443-020-00400-9. Epub 2021 Jan 22.