Product Overview

Avanafil (TA-1790, INN: Avanafil, (S)-4-[(3-Chloro-4-methoxybenzyl)amino]-6-[4-(hydroxymethyl)-1-piperidinyl]-2-(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide, CAS 330784-47-7, C23H26ClN7O3, MW 483.95 g/mol) is a second-generation, highly selective phosphodiesterase type 5 (PDE5) inhibitor developed by Mitsubishi Tanabe Pharma Corporation and FDA-approved in April 2012 under the brand name Stendra for the treatment of erectile dysfunction (ED). Avanafil represents the culmination of structure-based drug design targeting the PDE5 catalytic domain — its pyrimidine-carboxamide scaffold achieves a tighter, more specific fit to the PDE5 active site than the sulfonamide-based first-generation agents (sildenafil, vardenafil), resulting in sub-nanomolar affinity (IC50 for PDE5: ~5.2 nM) and exceptional isoform selectivity: PDE5/PDE6 ratio >1,000 (vs ~10 for sildenafil, ~25 for vardenafil) and PDE5/PDE1 ratio >100 (vs ~4 for sildenafil). These selectivity advantages translate directly into the clinic: avanafil produces virtually no PDE6-mediated visual disturbances (cyanopsia, photophobia — the “blue vision” side effect of sildenafil) and significantly fewer PDE1-mediated vasodilatory effects (flushing, headache, hypotension). The molecule’s pharmacokinetic profile is also differentiated: rapid GI absorption (tmax 30-45 min, the fastest of all oral PDE5 inhibitors), clinical onset within 15-30 minutes (sildenafil: 30-60 min; tadalafil: 60-120 min), moderate half-life of ~5 hours (shorter than tadalafil’s 17.5 h, enabling a defined on-demand window without next-day carryover), and low food interaction — avanafil absorption is not significantly affected by a moderate-fat meal (unlike sildenafil, which shows a 29% reduction in Cmax and a 60-minute Tmax delay). Avanafil is metabolized primarily via CYP3A4 (with minor contributions from CYP2C9) to four major inactive metabolites; concomitant strong CYP3A4 inhibitors (ketoconazole, ritonavir) require dose adjustment. The global PDE5 inhibitor market is valued at over $4 billion annually, with avanafil capturing an increasing share as generic entry expands patient access and physician familiarity grows. UPOR Biotech supplies avanafil pharmaceutical API at ≥99% HPLC purity, manufactured under full GMP ICH Q7 at ISO 9001:2015 certified, FDA-registered facilities, with Type II DMF support for ANDA filers in the US, EU, and other regulated markets.

As a leading avanafil API manufacturer and bulk supplier, UPOR Biotech provides high-purity (≥99% HPLC) avanafil powder for generic pharmaceutical companies, ANDA developers, contract manufacturing organizations (CMOs), and research institutions worldwide. Avanafil’s differentiated clinical profile — faster onset, superior selectivity, lower side-effect burden — positions it as a compelling ANDA opportunity with strong market differentiation against the crowded sildenafil and tadalafil generic fields. DMF Type II support with Letter of Authorization, complete ANDA documentation package, and flexible MOQ starting at 1 kg. Free sample available for qualified buyers. Every shipment includes full documentation: COA with HPLC impurity profile, MSDS, HPLC chromatogram, and ICH stability data.

Avanafil vs Sildenafil vs Tadalafil — Second-Generation PDE5 Selectivity: Why Avanafil Delivers Faster Onset with Fewer Off-Target Effects

Comparing the three leading oral PDE5 inhibitors reveals clinically meaningful differentiation — not just me-too interchangeability. Sildenafil (Viagra, 1998) is the first-generation sulfonamide-based PDE5 inhibitor with an IC50 of ~3.5 nM and 4-6 h efficacy window, but its PDE5/PDE6 selectivity ratio of only ~10 produces visual side effects (cyanopsia, photophobia) in 3-11% of patients, and its PDE5/PDE1 ratio of ~4 contributes to vasodilatory flushing and headache. Tadalafil (Cialis, 2003) has a unique methylenedioxyphenyl scaffold with a 17.5 h half-life enabling 36-hour efficacy and daily dosing — the best choice for patients desiring spontaneity — but its slow onset (tmax 2 h) limits on-demand convenience. Avanafil (Stendra, 2012) is the second-generation agent optimized by structure-based design: (1) Fastest onset — therapeutically effective in 15-30 min with tmax 30-45 min, roughly twice as fast as sildenafil. (2) Highest selectivity — PDE5/PDE6 ratio >1,000 (100× better than sildenafil), virtually eliminating visual disturbance risk; PDE5/PDE1 ratio >100, significantly reducing flushing. (3) Short, predictable half-life (~5 h) — an on-demand window without next-day carryover, unlike tadalafil’s 36-h duration. (4) Low food interaction — absorption unaffected by moderate-fat meals, unlike sildenafil’s 29% Cmax penalty. (5) Clean CYP profile — primarily CYP3A4; no active metabolites; no CYP2D6 interaction. The optimal patient-selection framework: avanafil for rapid-acting, low-side-effect on-demand therapy; tadalafil for spontaneous daily-dosing regimens; sildenafil as the cost-effective, extensively studied first-line option in price-sensitive markets. For ANDA developers, avanafil’s differentiated profile offers a premium generic positioning opportunity in the $4B+ PDE5 inhibitor market.

Technical Specifications

PropertySpecification
Product NameAvanafil — PDE5 Inhibitor Pharmaceutical API (≥99% HPLC, GMP ICH Q7)
INN / USANAvanafil
Brand NameStendra (US); Spedra (EU); Zepeed (South Korea)
Common Name / SynonymsAvanafil; TA-1790; (S)-4-[(3-Chloro-4-methoxybenzyl)amino]-6-[4-(hydroxymethyl)-1-piperidinyl]-2-(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide
CAS Number330784-47-7
Molecular FormulaC23H26ClN7O3
Molecular Weight483.95 g/mol
Pharmacological ClassPhosphodiesterase type 5 (PDE5) inhibitor — second-generation
Mechanism of ActionCompetitive, reversible, highly selective inhibition of cGMP-specific PDE5 in corpus cavernosum smooth muscle. Prevents cGMP hydrolysis, sustaining NO-mediated vasodilation and penile blood flow. PDE5 IC50: ~5.2 nM. Selectivity: PDE5/PDE6 >1,000; PDE5/PDE1 >100.
Key Clinical AdvantagesFaster onset (15-30 min vs 30-60 min sildenafil); highest PDE5 isoform selectivity (minimal visual/flushing side effects); rapid absorption (tmax ~30-45 min); short half-life (~5h) for defined on-demand window; low food interaction; metabolized primarily via CYP3A4
AppearanceWhite to off-white crystalline powder
Assay (HPLC, Anhydrous Basis)≥99.0%
Chiral Purity≥99.5% ee (S-enantiomer) by chiral HPLC
Total Related Substances≤1.0% (HPLC)
Any Single Impurity≤0.10% (ICH Q3A threshold)
IdentificationIR spectrum conforms to reference standard; HPLC retention time matches Avanafil RS; specific rotation [α]D20 conforms
Melting Point208 – 212°C
Specific Rotation[α]D20: +41.0° to +45.0° (c = 1.0, DMSO)
Water Content (Karl Fischer)≤1.0%
Loss on Drying≤1.0% (105°C, 2 hours)
Residue on Ignition≤0.1%
SolubilityPractically insoluble in water; sparingly soluble in ethanol and methanol; soluble in DMSO and DMF
Heavy Metals (Total)≤10 ppm (as Pb)
Elemental ImpuritiesPb ≤2 ppm; As ≤1 ppm; Hg ≤1 ppm; Cd ≤1 ppm; Class 1 and 2A metals per USP <232> / ICH Q3D compliant
Residual SolventsUSP <467> / EP <5.4> / ICH Q3C Class 3 compliant
Genotoxic ImpuritiesICH M7 compliant — nitrosamine risk assessment per FDA Guidance (February 2024); no nitrosamine impurities detected above AI limit
Microbial LimitsTAMC ≤100 CFU/g; TYMC ≤10 CFU/g (USP <61> / EP <2.6.12>); Pathogens (E. coli, Salmonella, S. aureus, P. aeruginosa) — Absent in 10 g (USP <62> / EP <2.6.13>)
Grade / StandardsPharmaceutical API Grade (≥99% HPLC); GMP ICH Q7; DMF Type II support available
DMFType II Drug Master File — Letter of Authorization (LoA) available for ANDA cross-reference
CertificationsISO 9001:2015, GMP ICH Q7, FDA Facility Registration, HALAL, KOSHER, Non-GMO, BSE/TSE-Free
StabilityReal-time: 36 months at 25°C/60%RH (ICH Q1A); Accelerated: 6 months at 40°C/75%RH. No significant degradation observed under either condition.
Packaging1 kg / 5 kg / 10 kg double-layer aluminum foil bags with PE liner under nitrogen blanket; 25 kg fiber drums with double PE liner and desiccant
Storage15 – 25°C, tightly sealed in original container, protect from light and moisture. Store under inert atmosphere (N2) after opening.
Shelf Life3 years from date of manufacture under recommended storage conditions

Key Benefits — Avanafil

Fastest-Onset Oral PDE5 Inhibitor — Clinically Effective in 15-30 Minutes

Avanafil reaches therapeutic plasma levels twice as fast as sildenafil (tmax 30-45 min vs 60 min), with clinical efficacy demonstrated within 15-30 minutes of oral administration. Rapid GI absorption is unaffected by moderate-fat meals — unlike sildenafil, which shows 29% Cmax reduction. Ideal for on-demand ED therapy requiring speed and predictability.

15-30 min Onset

Superior PDE5 Isoform Selectivity — 100× Fewer Off-Target Effects Than Sildenafil

PDE5/PDE6 selectivity ratio exceeds 1,000 (vs ~10 for sildenafil, ~25 for vardenafil) — virtually eliminating PDE6-mediated visual disturbances (cyanopsia, photophobia). PDE5/PDE1 ratio exceeds 100 — significantly reducing PDE1-mediated vasodilatory flushing and headache. The cleanest side-effect profile in the PDE5 inhibitor class.

>1,000× Selectivity

GMP ICH Q7 Manufacturing — ≥99% HPLC with Full ANDA Documentation Package

API manufactured under full GMP ICH Q7 at ISO 9001:2015 certified, FDA-registered facilities. Type II DMF with LoA for FDA ANDA cross-reference. Complete documentation: COA with impurity profile, HPLC chromatograms, ICH stability data, nitrosamine risk assessment (FDA Guidance), and genotoxic impurity assessment (ICH M7). Ready-to-file quality.

GMP + DMF

Differentiated Generic ANDA Opportunity — Premium Position in $4B+ PDE5 Market

Avanafil’s faster onset, superior selectivity, and cleaner side-effect profile support a premium generic positioning distinct from the crowded sildenafil and tadalafil fields. Growing global market share as patent expirations expand access. Low food interaction and short, predictable half-life (~5h) address key patient pain points with first-generation agents.

ANDA Ready

Applications

Generic Erectile Dysfunction Tablets — ANDA Development & Commercial Supply

Avanafil API at ≥99% HPLC purity for generic Stendra tablet development (50 mg, 100 mg, 200 mg). Type II DMF with LoA for ANDA Module 3.2.S cross-reference. Full CMC documentation package including impurity profile, stability data, and nitrosamine risk assessment per FDA Guidance. Flexible batch sizes from pilot to commercial scale.

Branded Pharmaceutical Manufacturing — Emerging Market Registration

GMP ICH Q7 avanafil API for branded product registration in emerging pharmaceutical markets (Latin America, MENA, ASEAN, CIS). Complete regulatory dossier support including DMF, CTD-quality documentation, and in-country filing assistance. OEM and contract manufacturing partnerships available with flexible MOQ starting at 1 kg.

Combination PDE5 Inhibitor Formulations — Fixed-Dose Development

Avanafil API for fixed-dose combination products with other ED or BPH therapeutics. Compatible with tadalafil (dual-PDE5 strategy), α-blockers, and 5α-reductase inhibitors. Custom particle size distribution and polymorph control for optimized formulation performance. Dedicated technical support for formulation development and bioequivalence studies.

Clinical Research & Bioequivalence Studies

High-purity (≥99% HPLC) avanafil API for pharmacokinetic, bioequivalence (BE), and clinical endpoint studies. Full characterization package: particle size distribution, polymorphic form (PXRD), DSC thermogram, specific rotation, and residual solvent profile. Available in research quantities (10 g to 500 g) with expedited shipping for time-sensitive BE study initiation.

Orally Disintegrating & Rapid-Dissolve Formulations

Avanafil’s rapid absorption profile (tmax 30-45 min) makes it an ideal candidate for orally disintegrating tablet (ODT), sublingual, and fast-dissolve film formulations. Custom micronization (D90 ≤ 10 µm) and polymorph control available to optimize dissolution kinetics. Technical support for taste masking, excipient compatibility, and accelerated BE study design.

Export to Regulated Markets — US FDA, EMA, PMDA, TGA, Health Canada

Full GMP ICH Q7 avanafil API certified for export to all major regulated markets. FDA-registered facility with successful customer ANDA approvals. EMA Written Confirmation (WC) support. PMDA Drug Master File registration (Japan MF). Health Canada DMF and TGA GMP Clearance available. Complete regulatory support from initial inquiry through commercial supply.

Frequently Asked Questions

Avanafil (TA-1790, CAS 330784-47-7, C23H26ClN7O3, MW 483.95 g/mol) is a second-generation, highly selective phosphodiesterase type 5 (PDE5) inhibitor FDA-approved in 2012 as Stendra for erectile dysfunction. PDE5 is the predominant cGMP-hydrolyzing enzyme in corpus cavernosum smooth muscle — it degrades cyclic guanosine monophosphate (cGMP), the second messenger that mediates nitric oxide (NO)-induced vasodilation. During sexual stimulation, NO released from cavernosal nerve terminals and endothelial cells activates soluble guanylyl cyclase, which synthesizes cGMP. Avanafil competitively binds to the PDE5 catalytic site, preventing cGMP hydrolysis. This sustains elevated cGMP levels, which in turn: (1) activates protein kinase G (PKG), (2) phosphorylates and opens potassium channels, (3) reduces intracellular calcium, and (4) relaxes cavernosal smooth muscle — dilating penile arterioles and increasing blood flow into the corpus cavernosum sufficient for erection. Avanafil’s pyrimidine-carboxamide scaffold achieves sub-nanomolar PDE5 affinity (IC50 ~5.2 nM) with exceptional isoform selectivity: the PDE5/PDE6 ratio exceeds 1,000 (vs ~10 for sildenafil), meaning virtually no retinal PDE6 inhibition and therefore no visual side effects (cyanopsia, photophobia — the “blue vision” effect of sildenafil). The PDE5/PDE1 ratio exceeds 100 (vs ~4 for sildenafil), significantly reducing PDE1-mediated vasodilation (flushing, headache, hypotension). Avanafil does not induce erection without sexual stimulation — it amplifies the endogenous NO-cGMP signal only when the NO pathway is activated by arousal. Metabolized primarily by CYP3A4 to four major inactive metabolites; concomitant strong CYP3A4 inhibitors require dose adjustment. UPOR Biotech supplies avanafil API at ≥99% HPLC purity under GMP ICH Q7 with Type II DMF support.

Avanafil, sildenafil, and tadalafil are all oral PDE5 inhibitors, but they differ in four clinically decisive dimensions — making them complementary tools rather than interchangeable commodities. (1) Onset of action: Avanafil is the fastest — tmax 30-45 minutes, therapeutically effective within 15-30 minutes. Sildenafil: tmax 60 minutes, clinical onset 30-60 minutes. Tadalafil: tmax 120 minutes, clinical onset 60-120 minutes. Avanafil is approximately twice as fast as sildenafil for therapeutic effect. (2) Isoform selectivity and side-effect profile: Avanafil has a PDE5/PDE6 selectivity ratio exceeding 1,000 — versus ~10 for sildenafil and ~25 for vardenafil. This means avanafil produces virtually no PDE6-mediated visual disturbances (cyanopsia, photophobia, blue-tinted vision — affecting 3-11% of sildenafil users). Avanafil’s PDE5/PDE1 ratio exceeds 100, versus ~4 for sildenafil, meaning significantly fewer PDE1-mediated vasodilatory effects (flushing, headache, hypotension). Tadalafil also has favorable selectivity but achieves it through a different scaffold (methylenedioxyphenyl vs avanafil’s pyrimidine-carboxamide). (3) Duration of action: Avanafil half-life is ~5 hours, providing a defined 4-6 hour on-demand window without next-day carryover — ideal for patients who want a short, predictable therapeutic window. Tadalafil half-life is 17.5 hours, enabling the unique 36-hour efficacy window and suitability for once-daily dosing (2.5-5 mg) — ideal for patients desiring spontaneity without planning. Sildenafil half-life is 3-5 hours, similar to avanafil but with slower onset and more side effects. (4) Food interaction: Avanafil absorption is not significantly affected by a moderate-fat meal — a critical practical advantage, since patients rarely take ED medication on an empty stomach. Sildenafil shows a 29% reduction in Cmax and a 60-minute delay in Tmax with a high-fat meal. Tadalafil absorption is unaffected by food. Clinical selection framework: avanafil for rapid-acting, low-side-effect on-demand therapy; tadalafil for spontaneous daily-dosing flexibility; sildenafil as the established, extensively studied first-line option. For ANDA developers, avanafil’s differentiated profile supports premium generic positioning distinct from the crowded sildenafil/tadalafil generic markets.

UPOR Biotech’s avanafil API meets the highest pharmaceutical purity and GMP standards. Every batch is manufactured under full GMP ICH Q7 compliance at ISO 9001:2015 certified, FDA-registered facilities. The release specification includes: Assay ≥99.0% (HPLC, anhydrous basis); chiral purity ≥99.5% ee (S-enantiomer by chiral HPLC); total related substances ≤1.0%; any single impurity ≤0.10% (per ICH Q3A); water content ≤1.0% (Karl Fischer); residue on ignition ≤0.1%; heavy metals ≤10 ppm; elemental impurities per USP <232> / ICH Q3D (Pb ≤2 ppm, As ≤1 ppm, Hg ≤1 ppm, Cd ≤1 ppm); residual solvents per USP <467> / ICH Q3C; genotoxic impurity assessment per ICH M7 with nitrosamine risk assessment per FDA Guidance (February 2024); and microbial limits per USP <61>/<62> (TAMC ≤100 CFU/g, TYMC ≤10 CFU/g, specified pathogens absent). The manufacturing process has been validated per ICH Q7 Section 12; critical process parameters and quality attributes are controlled through in-process testing and final release testing. Type II DMF is maintained with the US FDA and other regulatory agencies; a Letter of Authorization (LoA) is issued for ANDA cross-reference upon execution of a Mutual Confidentiality Agreement (MCA). Stability data includes 36-month real-time (25°C/60%RH) and 6-month accelerated (40°C/75%RH) protocols per ICH Q1A(R2). No significant degradation has been observed under either condition. Free sample (10 g) available for qualified buyers for characterization and method development.

UPOR Biotech provides a complete ANDA-support documentation package designed for seamless integration into Module 3.2.S (Drug Substance) of the Common Technical Document (CTD): (1) Type II Drug Master File (DMF) with Letter of Authorization (LoA) permitting FDA cross-reference. (2) Certificate of Analysis (COA) per batch — assay (≥99.0% HPLC), full impurity profile with RRT/RRF values, chiral purity (≥99.5% ee), water content, residual solvents, heavy metals, elemental impurities, and microbial panel. (3) Material Safety Data Sheet (MSDS/SDS) — GHS-compliant, 16-section format. (4) Signed and dated HPLC chromatograms with integration parameters, system suitability data, and reference standard traceability. (5) GMP Compliance Certificate (ICH Q7) with facility GMP status statement. (6) ISO 9001:2015 Certificate. (7) FDA Facility Registration Number. (8) BSE/TSE-Free Statement. (9) Nitrosamine Risk Assessment Report per FDA Guidance (February 2024) — confirming no nitrosamine impurities detected above the acceptable intake (AI) limit for the avanafil nitrosamine drug substance-related impurity (NDSRI). (10) Genotoxic Impurity Assessment per ICH M7 with purge factor calculations and supporting analytical data. (11) Elemental Impurities Compliance Statement (ICH Q3D). (12) Residual Solvents Statement (ICH Q3C Class 3). (13) Stability Data Package — real-time (36-month, 25°C/60%RH) and accelerated (6-month, 40°C/75%RH) with trend analysis per ICH Q1A(R2) and Q1E. (14) Forced Degradation Study Report — acid, base, oxidative, thermal, photolytic (ICH Q1B) — supporting the stability-indicating nature of the HPLC method. (15) Complete Lot Traceability Documentation from starting material through intermediate to finished API, including supply chain audit trail. All documents are provided in English. Additional regulatory support (Japanese MF, EMA ASMF, Health Canada DMF, TGA GMP Clearance) available upon request.

UPOR Biotech holds and provides the following certifications applicable to avanafil API: ISO 9001:2015 (Quality Management Systems), GMP ICH Q7 (Active Pharmaceutical Ingredient Good Manufacturing Practices), FDA Facility Registration (US Food and Drug Administration), HALAL Certificate (compliant with Islamic dietary and pharmaceutical requirements), KOSHER Certificate (compliant with Jewish dietary and pharmaceutical requirements), Non-GMO Statement, BSE/TSE-Free Statement, Allergen Statement, Nitrosamine Risk Assessment per FDA/EMA Guidance, and ICH M7 Genotoxic Impurity Assessment. Our manufacturing facilities undergo regular audits by customers, regulatory agencies, and third-party certification bodies. Every shipment of avanafil API includes the complete compliance documentation package tailored to the destination market’s regulatory requirements. MOQ: 1 kg for commercial orders; 10 g for R&D characterization and method development samples. Free sample available for qualified B2B buyers upon request — contact our sales team with your company profile, intended application, and target market. All documents are provided in English; certified translations available for specific regulatory submissions (Spanish, Portuguese, Arabic, Japanese, Korean). For ANDA filers, we offer dedicated regulatory affairs support throughout the submission and review cycle.