Stendra (avanafil) / IEH Biopharma, JW Pharma, Menarini, Endo - LARVOL DELTA

Energetic compensation at a cost: hypermetabolism in human motor neurons with ATP synthase deficiency (SSIEM 2026) - "Consistent with this, treatment with avanafil did not significantly alter metabolites levels...Although the precise heteroplasmy levels in patient motor neurons remain unknown, our findings indicate that motor neurons can sustain ATP production through extensive metabolic adaptation to OxPhos dysfunction caused by the MT-ATP6 mutation. However, this adaptation comes at a cost, revealing metabolic vulnerabilities that may contribute to neuronal dysfunction in ATP synthase deficiency."

Ataxia • CNS Disorders • Glomerulonephritis • IgA Nephropathy • Metabolic Disorders • Movement Disorders • Renal Disease

Analytical strategies for identifying PDE5 inhibitors in damiana (Turnera diffusa) products. (PubMed, J Chromatogr A) - "This study presents the development and validation of three analytical methods (LC-DAD, LC-Q MS, and FIA-ToF MS) for the sensitive detection and accurate quantitation of four PDE5i (avanafil, vardenafil, sildenafil, and tadalafil) in damiana-based food supplements. None of the four PDE5i were detected in the 20 damiana supplements analyzed. Nevertheless, this methodology offers a rapid and reliable screening tool for the routine analysis of these commercial products in quality control and regulatory laboratories, contributing to adulteration detection, consumer safety and regulatory enforcement."

Journal

A comparative evaluation of on-demand phosphodiesterase-5 inhibitor efficacy in erectile dysfunction treatment: a systematic review and network meta-analysis of double-blind, placebo-controlled, randomized trials. (PubMed, J Sex Med) - "PDE5is are highly effective, with sildenafil showing a significantly greater efficacy compared with the other PDE5is."

Clinical • Journal • Retrospective data • Review • Erectile Dysfunction

Reduction in All-Cause Mortality with Daily Tadalafil Over Three Years: Real-World Evidence (AUA 2026) - "Those who take PDE5 inhibitor (Sildenafil, Tadalafil 10 mg or 20 mg, Vardenafil, and Avanafil) on demand was defined as Group Demand. Regular low-dose Tadalafil use after ED diagnosis significantly reduced 3-year all-cause mortality and MACE, suggesting cardiovascular benefits beyond erectile function."

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Coronary Artery Disease • Erectile Dysfunction • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PDE5 Inhibitors and Cardiovascular Outcomes in Men with ED: Propensity-Weighted Hazard Ratios over 12 Months (AUA 2026) - "Those started taking PDE5 inhibitor (Sildenafil, Tadalafil, Vardenafil, and Avanafil) within one month since ED diagnosed was defined as Group A. Those who did not take PDE5 inhibitor was defined as Group B. Outcomes were assessed from day 1 to day 365 after the index event. Begin to take PDE5 inhibitor within 1 month once ED diagnosed has significant efficacy in lowering hazard ratio of 1-year all-cause mortality and MACE. It is worth noted that its protective effect still presents in those with systematic diseases."

Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • Coronary Artery Disease • Erectile Dysfunction • Heart Failure • Immunology • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases

Repurposing of drug molecules targeting protease and helicase domain of Dengue virus NS3 protein: a virtual screening approach. (PubMed, In Silico Pharmacol) - "Finally, two compounds, DB06237 (Avanafil) and DB11262 (Bisoctrizole) were selected for further studies based on computational analyses...This study may provide an insight for utilizing small molecule inhibitors for the pharmacological development and repurposing of established drugs to curb the fatal consequences of dengue virus infection. The online version contains supplementary material available at 10.1007/s40203-026-00643-2."

Journal • Dengue Fever • Infectious Disease

In brief: Vybrique - sildenafil oral film for erectile dysfunction. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Erectile Dysfunction

Therapeutic Repurposing of Avanafil Against Lipopolysaccharide-induced Depression and Autoimmune Hepatitis: Gut-brain-liver Axis Orchestration Via Regulation of TLR4/NF-κB/IDO and Nrf2/HO-1 Pathways. (PubMed, Mol Neurobiol) - "Mechanistically, AVA downregulated the TLR4/NF-κB/IDO pathway, restored serotonin levels, reduced quinolinic acid accumulation, and activated the Nrf2/HO-1 signaling cascade in both hippocampal and liver tissues. These findings suggest that AVA exerts neuroprotective and hepatoprotective effects by modulating intestinal permeability, inflammation, and oxidative stress, making it a promising therapeutic candidate for conditions associated with systemic inflammation such as MDD and AIH."

Journal • Autoimmune Hepatitis • CNS Disorders • Depression • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Liver Failure • Major Depressive Disorder • Mood Disorders • Oncology • Psychiatry • IL1B • IL6 • MMP9 • TJP1 • TLR4 • TNFA

Capillary electrophoresis-contactless conductivity detection for routine screening of PDE-5 inhibitor adulterants in sexual-enhancement supplements. (PubMed, Anal Methods) - "A capillary electrophoresis method with capacitively coupled contactless conductivity detection (CE-C4D) was developed for simultaneous determination of sildenafil, homosildenafil, hydroxyhomosildenafil, and avanafil. Results agreed with the reference LC-MS/MS method, with deviations below 10%. These findings support CE-C4D as a practical first-tier tool for regulatory screening of PDE-5 inhibitor adulteration in health supplements."

Journal

Comparison of Safety and Efficacy of Avanafil and Tadalafil in the Treatment of Erectile Dysfunction: A Prospective Observational Study. (PubMed, Cureus) - "Conclusion Tadalafil demonstrated slightly better efficacy in improving erectile function compared to Avanafil, although both drugs were effective and well-tolerated. The choice of treatment should consider patient preferences and specific clinical contexts, as both medications offer significant benefits with minimal risk of severe adverse effects. Both PDE-5 inhibitors were effective based on patient-reported outcomes, although objective rigidity was not measured."

Journal • Observational data • Erectile Dysfunction

A systematic review of regulatory approved drugs and pharmacological interventions for erectile dysfunction. (PubMed, J Pharm Pharmacol) - "In summary, this review helps doctors and researchers by providing clear information about PDE5 inhibitor drugs for ED and pointing out areas where more research can improve treatment and quality of life for men with this condition."

Journal • Cardiovascular • Erectile Dysfunction

Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential. (PubMed, Bone Rep) - "In preclinical models, inhibitors that target PDE3 (e.g., cilostazol, milrinone), PDE4 (roflumilast, apremilast), and PDE5 (e.g., sildenafil, avanafil, vardenafil) exhibit promising anabolic, anticatabolic, and anti-inflammatory effects on skeletal tissues. Broad-spectrum inhibitors such as pentoxifylline and dipyridamole also demonstrate dual benefits in terms of bone regeneration and joint preservation...Understanding the mechanism of action of PDE inhibitors can facilitate their translation into the clinic, help with their application in combined therapies, or minimize their potential adverse effects. This approach offers a cost-effective and viable path toward novel therapies for musculoskeletal health."

Journal • Review • Cardiovascular • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Osteoarthritis • Osteoporosis • Pain • Rheumatoid Arthritis • Rheumatology

Associations between phosphodiesterase type 5 inhibitors and vascular function: a systematic review and meta-analysis on randomized-controlled trials. (PubMed, Syst Rev) - "Compared with the placebo, PDE5is improved vascular parameters, indicating the potential of PDE5is for treating subclinical cardiovascular diseases. Further research is needed to confirm the role of the improvement on vascular parameters by PDE5isin preventing and treating cardiovascular diseases."

Journal • Retrospective data • Review • Cardiovascular • Erectile Dysfunction

Metabolic costs and trade-offs of hypermetabolism in human motor neurons with ATP synthase deficiency. (PubMed, Commun Biol) - "Mitochondrial membrane potential and coupling efficiency remained stable, and the therapeutic agent avanafil did not affect metabolite levels. However, a redistribution of acetyl-CoA usage resulted in metabolic trade-offs, including reduced histone acetylation and altered maintenance of the neurotransmitter acetylcholine, revealing potential vulnerabilities in motor neurons. These findings advance the understanding of cellular metabolic consequences imposed by hypermetabolic conditions."

Journal

Hyperprolactinemia-associated erectile dysfunction: retrospective cohort evaluating the effect of prolactin normalization on IIEF-5. (PubMed, Neuro Endocrinol Lett) - "Our results confirmed the positive impact of resolving the primary endocrine cause on overall sexual health. These findings underscore the importance of comprehensive hormonal assessment in the management of male sexual dysfunction, including measurement of PRL levels. While hyperprolactinemia is a relatively uncommon cause of ED, its treatment-whether pharmacological or surgical-can lead to PRL normalization and a marked improvement in erectile function. The combined use of PDE5I and hyperprolactinemia treatment represents an effective therapeutic approach that should be considered in the care of men with ED."

Journal • Retrospective data • Endocrine Cancer • Endocrine Disorders • Erectile Dysfunction • Sexual Disorders • PRL

Oral drug treatments of erectile dysfunction: a AFU/SFMS systematic review. (PubMed, Fr J Urol) - "PDE5Is are effective first-line treatments for ED, with similar efficacy and safety profiles. The choice of PDE5I should be tailored to the patient's needs, comorbidities, and lifestyle preferences. Future studies should address specific subpopulations to optimize clinical practice guidelines."

Journal • Review • Back Pain • Dyspepsia • Erectile Dysfunction • Genito-urinary Cancer • Infectious Disease • Musculoskeletal Pain • Oncology • Pain • Prostate Cancer • Solid Tumor

Toward Natural Products-Based Drug Development for Erectile Dysfunction: A Molecular Candidate from Plant Tribulus terrestris Identified by an Integrated In Silico Study. (PubMed, OMICS) - "Conventional pharmacological interventions for erectile dysfunction (ED) primarily rely on the phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, tadalafil, vardenafil, and avanafil that have side effects despite their therapeutic effects. Importantly, diosgenin,dehydro, a saponin obtained from T. terrestris, was identified as a particularly promising candidate for PDE5 inhibition by virtue of its higher negative binding affinity and, therefore, displaying a potential in drug discovery and development for ED. In addition, in silico pharmacokinetic analysis and toxicity assessments support the prospects of these T. terrestris-derived phytochemicals for future in vitro and in vivo research for innovation in ED therapeutics."

Journal • Erectile Dysfunction

Ameliorative Role of Phosphodiesterase-5 (PDE-5) Inhibitor "Avanafil" via Modulating cAMP & cGMP Pathway Against Alzheimer's Disease. (PubMed, Neurochem Res) - "Histopathological changes by H&E staining showed significant difference in treatment vs. toxic rats. The current investigation suggested that Avanafil improves memory by improving cAMP and cGMP pathways, implying that it may have therapeutic prospective in cognitive deficiencies linked with Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Oncology • Pain • BDNF • IL1B • IL6 • TNFA

Experimental and computational approaches for evaluating molecule interactions with equilibrative nucleoside transporters 1 and 2. (PubMed, J Pharmacol Exp Ther) - "This resulted in the identification of the Food and Drug Administration-approved drugs isradipine, avanafil, and istradefylline as inhibitors of ENT1. We have screened over 1600 diverse molecules, allowing us to build machine learning models that in turn were further used to make predictions to validate the models. Our combined experimental and machine learning approach resulted in the identification of multiple Food and Drug Administration-approved medications as inhibitors of ENT1 or ENT2."

Journal • Infectious Disease • Oncology • SLC29A1 • SLC29A2

Synergy between oral PDE5 inhibitors and topically applied nitric oxide microparticles on the erectile response in a rat model of cavernous nerve injury. (PubMed, Int J Impot Res) - "One week post-surgery animals were administered PDE5i via oral gavage (sildenafil 0.05 mg/kg (N = 9), tadalafil 0.005 mg/kg (N = 8), vardenafil 0.01 mg/kg (N = 7), avanafil 0.1 mg/kg (N = 8) or untreated (N = 5) followed by topical application of 250 mg NO-MP to the penile dermis. No significant changes in maximal ICP/BP, duration of erectile response or baseline ICP/BP were observed. These results suggest that combining NO-MP with PDE5i may provide a promising approach for treating ED after radical prostatectomy."

Journal • Preclinical • Erectile Dysfunction

Reducing Contrast-Induced Nephropathy Risk in a Murine Model: Role of Avanafil and Vardenafil in Modulating Oxidant/Antioxidant Balance. (PubMed, Cureus) - "The treatment groups with VAR, AVA, and NAC were noted with higher values of TAC, CAT, and GSH, while lower values of TBARS and PROTC indicated a protective effect against oxidative injury. The findings indicate that VAR and AVA effectively control the oxidant/antioxidant status, preventing oxidative stress and the incidence of CIN. Further research would be required to replicate these findings and identify the therapeutic potential of VAR and AVA in clinical conditions."

Journal • Preclinical • Nephrology • Renal Disease • CAT

Presence of Sildenafil and Tadalafil in Herbal Medicinal Products Claimed to Treat Erectile Dysfunction in Nyamagana and Ilemela Districts, Mwanza, Tanzania. (PubMed, Biomed Res Int) - "Phosphodiesterase type 5 inhibitors (PDE 5is) such as sildenafil citrate, tadalafil, vardenafil hydrochloride, and avanafil are synthetic oral medications approved for ED treatment. Aphrodisiac-claimed herbal medicinal products are adulterated with conventional medicines, sildenafil and tadalafil. Alarmingly, some of these products contain higher amounts of these pharmaceutical agents beyond the maximum daily dose."

Journal • Erectile Dysfunction

Assessing post-marketing safety of PDE5Is in erectile dysfunction: real-world evidence from the FDA adverse event reporting system. (PubMed, Asian J Androl) - "The U.S. Food and Drug Administration (FDA) has approved phosphodiesterase type 5 inhibitors (PDE5Is), including sildenafil, tadalafil, vardenafil, and avanafil, for treating ED. We detected AEs related to the nervous, cardiovascular, and ocular systems that were not listed on the labels of the four PDE5Is, warranting further research on the underlying mechanisms. Additionally, significant differences in PDE5I-associated AEs were observed across age, weight, and onset time, highlighting the need for tailored patient management."

Adverse events • HEOR • Journal • P4 data • Real-world evidence • Cardiovascular • Erectile Dysfunction

Impact of Second-Generation PDE 5 Inhibitor, Avanafil, on Retinal Function: Studies From Ex Vivo ERG. (PubMed, Invest Ophthalmol Vis Sci) - "This study demonstrated that avanafil does not inhibit spontaneous PDE6 activity, and it has a lower inhibitory effect on light-activated PDE6 compared to other PDE5 inhibitors like sildenafil and zaprinast. Additionally, we conclude that avanafil primarily impacts photoreceptor cells, with no significant direct effect on rod bipolar cell signaling. This study provides quantitative insights into avanafil's impact on retinal function, supporting the hypothesis that it has reduced off-target effects on PDE6 and retinal signaling."

Journal • Preclinical • CNS Disorders

Avanafil use in patients with erectile dysfunction and co-morbidities: Clinical insights from multiple aetiologies - A case series. (PubMed, Malays Fam Physician) - "No adverse events were reported among the patients. Avanafil is considered a potentially safe and effective treatment option for ED, particularly in individuals with co-morbidities."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Erectile Dysfunction • Hypertension • Metabolic Disorders