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

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

Patient Out-of-Pocket Costs for Guideline-Recommended Treatments for Erectile Dysfunction: A Medicare Cost Modeling Analysis (AUA 2025) - "Among PDE5i, avanafil is associated with highest annual OOP cost ($3,455), followed by vardenafil ($2,102), tadalafil ($723), and sildenafil ($459). PDE5i and IPP are cost-effective options with strong guideline recommendations. Better understanding of financial burden may improve shared decision making with ED patients."

Clinical • HEOR • Medicare • Reimbursement • US reimbursement • Erectile Dysfunction • Urology

From Oral to Sublingual: A Redefined Avanafil Tablet with a Breakthrough in Bioavailability and First-Pass Metabolism Avoidance. (PubMed, Drug Des Devel Ther) - "The sublingual tablets of the solubility-enhanced HP-β-CD-AVA inclusion complex represent a promising strategy to improve AVA bioavailability and bypass the first-pass effect. Furthermore, their extended activity offers potential clinical benefits, particularly for ED patients, such as ease of administration and reduced side effects."

Journal • Erectile Dysfunction

Novel spectrophotometric methods for concurrent assessment of duloxetine and avanafil in their binary mixture using derivative spectroscopy: greenness-blueness evaluation. (PubMed, BMC Chem) - "Furthermore, three current ecological tools namely the Eco-Scale, GAPI, and AGREE were used to evaluate the proposed method's greenness. The sustainability characteristics of the proposed method were also assessed using the Blue Applicability Grade Index (BAGI), a recently developed metric for assessing the practicality (blueness) of procedures."

Journal • Sexual Disorders

Effect of long and short half-life PDE5 inhibitors on HbA1c levels: a systematic review and meta-analysis. (PubMed, EClinicalMedicine) - "Among 1096 studies identified, in analysis of 13 studies with 1083 baseline patients, long half-life PDE5 inhibitors (tadalafil, PF-00489791) had decreases in HbA1c while short half-life PDE5 inhibitors (sildenafil, avanafil) had no change. This suggests future investigation into PDE5 inhibitors as part of combination therapy or as therapy for high HbA1c individuals is needed, especially because of variable risk of biases, homogeneity, and sample sizes in our study. None."

Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Avanafil Mitigates Testicular Ischemia/Reperfusion Injury via NLRP3 Pathway Modulation in Rats. (PubMed, Reprod Sci) - "It was found that avanafil can reduce the damage caused by testicular I/R and that it will find new applications in the future with the support of advanced experimental and clinical studies."

Journal • Preclinical • Cardiovascular • Oncology • Reperfusion Injury • IL1B • NLRP3 • TNFA

Phosphodiesterase-5 inhibitors and hearing impairment: a disproportionality analysis using the US food and drug administration adverse event reporting system. (PubMed, Expert Opin Drug Saf) - "Avanafil exhibited the strongest signal (ROR: 4.35, 95% CI: 2.56-7.41, IC: 2.09, 95% CI: 0.10-3.51), while vardenafil showed the weakest signal (ROR: 2.69, 95% CI: 2.21-3.28, IC: 1.14, 95% CI: 0.74-2.04). Sildenafil had the highest reported cases (ROR: 3.03, 95% CI: 2.82-3.24, IC: 1.57, 95% CI: 1.34-1.80). These findings highlight a significant correlation between PDE-5i use and HIAEs, emphasizing the need for careful evaluation in clinical practice and providing appropriate guidance to patients before initiating treatment."

Adverse events • Journal

Fast and simple voltammetric sensing of avanafil in the pharmaceutical formulation by using unmodified boron-doped diamond electrode. (PubMed, ADMET DMPK) - "The accuracy of the approach was demonstrated by comparing the results obtained using the developed method with those achieved using the UV-Vis spectrometry method. Our method simplifies the analytical process by eliminating the need for electrode modification, reducing both time and resource requirements while enhancing overall feasibility."

Journal • Erectile Dysfunction

Ionic-liquid/Carbowax 20 M functionalized capsule phase microextraction platform for the extraction of phosphodiesterase-5 inhibitors from human serum and urine prior to their determination by LC-MS. (PubMed, J Chromatogr A) - "Herein we describe the encapsulation of an ionic liquid (IL)/Carbowax 20M-functionalized sol-gel sorbent (sol-gel IL/Carbowax 20 M) in the lumen of porous polypropylene tubes for the capsule phase microextraction of three phosphodiesterase-5 inhibitors namely avanafil, sildenafil, and tadalafil in human serum and urine samples. The optimized CPME protocol exhibited reduced consumption of organic solvent and generation of waste, cost-effectiveness, and simplicity. Finally, the proposed method was successfully applied to the analysis of sildenafil in human urine after administration of drug-containing formulation."

Journal

Synthesis and mutagenic risk of avanafil's potential genotoxic impurities. (PubMed, RSC Adv) - "In the Ames test of Imp-E and Imp-F, in the dose range of 62.5-1000 μg per plate, with or without the presence of metabolic activation system S9, the number of revertant colonies did not exceed 2 times the number of colonies in the solvent control group and did not show a dose-response relationship, and the test results were negative. Imp-E and Imp-F were determined to be negative for genotoxicity, which could be controlled as class 5 in ICH M7, that is, non mutagenic impurity."

Journal

Phosphodiesterase (PDE) inhibition as a pharmacological option in OAB therapy: New molecular biological and functional aspects (NORDKONGRESS 2024) - "Contents Introduction: Phosphodiesterases (PDE) are key enzymes in the control of numerous organ and tissue functions, in urology the use of selective inhibitors of phosphodiesterase 5 (PDE5) in the indications Erectile Dysfunction (ED) (Avanafil, Sildenafil, Tadalafil, Vardenafil) and LUTS /BPS (Tadalafil) established...The organ bath technique was used to investigate the effects of selective inhibitors of PDEn 1, 2, 3 and 5 on the tonic contraction of isolated detrusor muscles induced by the muscarinic agonist carbachol (1 µM)...The results are in accordance with the hypothesis of a relevance of PDE isoenzymes 1 and 5 in the control of detrusor muscle function. The use of clinical models can clarify whether this group of substances can have practical significance in the future in the treatment of hypertonic disorders of urinary bladder function."

Erectile Dysfunction • Urology

Simultaneous measurement of duloxetine hydrochloride and avanafil at dual-wavelength using novel ecologically friendly TLC-densitometric method: application to synthetic mixture and spiked human plasma with evaluation of greenness and blueness. (PubMed, BMC Chem) - "Moreover, the proposed technique was evaluated in terms of greenness using four contemporary ecological metrics: The Analytical Greenness software (AGREE), the Green Analytical Procedure Index (GAPI), Eco-Scale, and the National Environmental Method Index (NEMI). Additionally, the Blue Applicability Grade Index (BAGI), a newly developed tool for evaluating the practicality (blueness) of procedures, was taken into consideration when evaluating the sustainability levels of the established approach."

Journal • CNS Disorders • Depression • Psychiatry

Phosphodiesterase type 5 inhibitors related hearing impairment: a real world study based on the FDA adverse event reporting system. (PubMed, Sci Rep) - "Reports for all the drugs indicated an increase since 2008, except for avanafil. This study showed that the disability rates of PDE5Is were 8.14-40%, the rates of initial or prolonged hospitalization were 6.21-10.24%, and the rates of required intervention were 3.31-9.45%. The pharmacovigilance study identified a potential risk of hearing impairment associated with PDE5Is, indicating the need for continuous monitoring and appropriate management."

Adverse events • Journal • Real-world • Real-world evidence

Inflammation in cerebral ischemia reperfusion improved by avanafil via nod-like receptor protein-3 inflammasome: an experimental study in rats. (PubMed, Brain Inj) - "Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1β, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil."

Journal • Preclinical • Cardiovascular • Inflammation • Reperfusion Injury • IL1B • NLRP3 • TNFA