Aventy

Approved Indications:

• Erectile Dysfunction (ED): Treatment of erectile dysfunction in adult males, including mild, moderate, and severe forms, to improve erectile function regardless of underlying etiology (psychogenic, organic, or mixed).

Clinically Accepted Off-label Uses (Limited):

• Although primarily indicated for ED, PDE5 inhibitors like avanafil have been explored for off-label use in:
• Pulmonary arterial hypertension (PAH) (investigational only)
• Raynaud’s phenomenon (limited and unapproved use)

Note: These off-label uses are better supported with other PDE5 inhibitors (e.g., sildenafil), and avanafil is not commonly recommended for them.

Route of Administration: Oral only (film-coated tablets)

Recommended Adult Dosage:

• Starting dose: 100 mg taken approximately 15–30 minutes before sexual activity.
• Adjustments:
• May increase to 200 mg or decrease to 50 mg depending on efficacy and tolerability.
• Maximum frequency: Once daily.
• With or without food: Can be taken with or without food; however, a high-fat meal may delay onset slightly.
• Onset of action: As early as 15 minutes; effective for up to 6 hours.

Pediatric Use:

• Not indicated and contraindicated in patients under 18 years.

Geriatric Use:

• No dosage adjustment necessary. However, elderly may show increased sensitivity to the drug.

Renal Impairment:

• Mild to moderate (eGFR ≥30 mL/min/1.73 m²): No adjustment needed.
• Severe renal impairment or dialysis patients: Use with caution; limited clinical data; avoid if not necessary.

Hepatic Impairment:

• Mild to moderate (Child-Pugh A and B): Start at 50 mg; increase only with caution.
• Severe hepatic impairment (Child-Pugh C): Use is not recommended.

Avanafil is a selective phosphodiesterase type 5 (PDE5) inhibitor. It works by blocking the degradation of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the penis. Sexual stimulation leads to nitric oxide (NO) release, which increases cGMP levels and causes smooth muscle relaxation and vasodilation, allowing increased blood flow to the penis and facilitating erection. By inhibiting PDE5, avanafil prolongs the action of cGMP, enhancing erectile response in the presence of sexual stimulation.

• Absorption: Rapidly absorbed after oral administration.
• Bioavailability: Not established, but systemic exposure increases proportionally with dose.
• Onset of Action: ~15 minutes (fastest among PDE5 inhibitors).
• Peak Plasma Concentration (Tmax): ~30–45 minutes
• Duration of Action: Up to 6 hours.
• Distribution: Volume of distribution ~105 L
• Protein Binding: ~99%
• Metabolism: Primarily hepatic via CYP3A4 (major) and CYP2C9 (minor)
• Active Metabolites: Yes (M4 metabolite, ~23% activity of parent drug)
• Half-life: Approximately 5 hours
• Elimination: Primarily through feces (~63%) and urine (~21%)

Pregnancy:

• Not indicated for use in females.
• Animal reproduction studies have not shown fetal harm at therapeutic exposures.
• FDA Pregnancy Category: Not assigned under current labeling. Avanafil is not intended for use in women.

Lactation:

• Not recommended or indicated for breastfeeding women.
• Unknown whether avanafil is excreted into human milk.
• Not studied in lactating females.

• Primary Class: Erectile Dysfunction Agent
• Subclass: Phosphodiesterase Type 5 (PDE5) Inhibitor
• Generation: Second-generation PDE5 inhibitor (with faster onset and improved selectivity)

• Known hypersensitivity to avanafil or any component of the formulation.
• Concomitant use with nitrates (e.g., nitroglycerin, isosorbide dinitrate) due to risk of severe hypotension.
• Use with guanylate cyclase stimulators (e.g., riociguat).
• Severe hepatic impairment (Child-Pugh C)
• Patients advised against sexual activity (e.g., due to unstable cardiovascular conditions)

• Cardiovascular Risk: Use with caution in patients with history of myocardial infarction, stroke, arrhythmias, or uncontrolled hypertension. Sexual activity may pose a cardiac risk.
• Priapism: Rare but serious; if erection lasts >4 hours, seek emergency care.
• Visual disturbances: Risk of non-arteritic anterior ischemic optic neuropathy (NAION). Discontinue if sudden vision loss occurs.
• Hearing loss: Sudden decrease or loss of hearing reported; discontinue if occurs.
• Hypotension: Particularly in combination with antihypertensives or alcohol.
• CYP3A4 Inhibitors: Use caution or avoid with strong inhibitors (see interactions).
• Anatomical deformation of penis: Caution in patients with conditions such as Peyronie’s disease.

Common Adverse Effects (≥1%):

• Headache
• Flushing
• Nasal congestion
• Back pain
• Dizziness
• Nausea

Less Common/Occasional:

• Vision changes (color tinge, blurred vision)
• Palpitations or tachycardia
• Gastrointestinal upset

Serious/Rare Adverse Effects:

• Priapism (erection >4 hours)
• Sudden vision loss (NAION)
• Sudden hearing loss
• Hypotension or syncope
• Myocardial infarction (rare, mainly in those with existing cardiac disease)

Onset & Dose-dependence:

• Adverse effects often dose-related and transient.
• Typically appear within 1 hour of dosing and resolve as drug levels decline.

Major Drug-Drug Interactions:

• Nitrates (all forms): Contraindicated – severe hypotension risk.
• Alpha-blockers: Risk of hypotension; separate doses by at least 4–6 hours.
• CYP3A4 Inhibitors:
• Strong inhibitors (e.g., ketoconazole, ritonavir, clarithromycin): Avoid use or reduce dose to 50 mg no more than once every 72 hours.
• Moderate inhibitors (e.g., erythromycin): Consider 50 mg once daily.
• CYP3A4 Inducers (e.g., rifampin, carbamazepine): May reduce avanafil efficacy.
• Alcohol: May potentiate hypotensive effects.

Food Interactions:

• High-fat meals may delay absorption but do not reduce effectiveness.

Metabolic Pathway:

• Mainly via CYP3A4, with minor involvement of CYP2C9.

• No recent changes to FDA-approved indications or major clinical guideline revisions.
• Avanafil continues to be recommended in AUA and EAU guidelines as a first-line treatment for erectile dysfunction.
• Recognized for fast onset and better side effect profile compared to earlier PDE5 inhibitors.
• Ongoing trials are evaluating its role in female sexual arousal disorder and pulmonary hypertension, though not approved.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Allowable excursions: 15°C to 30°C (59°F to 86°F)
• Humidity: Store in a dry place; avoid high humidity.
• Light protection: Keep in original packaging to protect from moisture and light.
• Handling: No refrigeration or reconstitution required. Keep out of reach of children.