Avanafil

Avanafil is a potent and rapidly acting PDE5 inhibitor used for the treatment of erectile dysfunction. It works by inhibiting the PDE5 enzyme, which increases cGMP levels in the corpus cavernosum during sexual stimulation, leading to smooth muscle relaxation and increased blood flow to the penis, facilitating erection.

Avanafil has a faster onset of action (15-30 minutes) compared to other PDE5 inhibitors and a half-life of approximately 5 hours. It can be taken with or without food, and its absorption is not significantly affected by high-fat meals.

The recommended starting dose is 100 mg, which can be adjusted between 50 mg and 200 mg based on efficacy and tolerability. Maximum dose is one tablet per day.

• Erectile Dysfunction

Avanafil is a selective phosphodiesterase type 5 (PDE5) inhibitor. During sexual stimulation, nitric oxide (NO) is released in the corpus cavernosum, which activates guanylate cyclase and increases cyclic guanosine monophosphate (cGMP) production. cGMP causes smooth muscle relaxation and increased blood flow, leading to erection. Avanafil inhibits PDE5 enzyme, preventing cGMP degradation, thereby prolonging erection.

Avanafil is rapidly absorbed, reaching peak plasma concentration (Tmax) in approximately 0.5-1 hour. It is primarily metabolized in the liver by CYP3A4 enzyme.

Avanafil irreversibly inhibits the PDE5 enzyme, preventing the breakdown of cGMP. During sexual stimulation, nitric oxide-mediated cGMP production increases, and avanafil prolongs its duration, which enhances vasodilation and blood flow to the penis, helping to maintain an erection.

Recommended Dose:

• Starting dose: 100 mg, taken 15-30 minutes before sexual activity.
• Dose Adjustment: Based on efficacy and tolerability, can be adjusted to 50 mg (30 minutes before) or 200 mg (15 minutes before).
• Maximum dose: Not to exceed 1 dose per day.
• Mild-moderate hepatic/renal impairment: No dose adjustment needed.
• Severe hepatic/renal impairment (CrCl 15-29 mL/min): Do not use (safety and efficacy not established).

With moderate CYP3A4 inhibitors: Dose should not exceed 50 mg/24 hours.

May be taken with or without food. Take orally 15-30 minutes before sexual activity. Do not take more than once daily.

If you miss a dose, it is taken as needed before sexual activity. A regular dosing schedule is not applicable. Do not take more than one dose per day.

Common (>2%):

• Headache (5.6%)
• Flushing (3.5%)
• Nasopharyngitis (3.4%)
• Back pain (2.5%)
• Nasal congestion (2.1%)

Less than 2%:

• Bronchitis, Influenza, Sinusitis, Sinus congestion, Hypertension, Dyspepsia, Nausea, Constipation, Rash

Less than 1%:

• Peripheral edema, Fatigue, Angina, Deep vein thrombosis, Palpitations, Gastritis, GERD, Hypoglycemia, Hyperglycemia, Depression, Insomnia, Cough, Dyspnea, Pruritus, Urinary tract infection, Increased erection, etc.

Serious Precautions:

• Patients with underlying cardiovascular conditions may have cardiovascular risk during sexual activity.
• Monitor patients with left ventricular outflow obstruction (e.g., aortic stenosis, hypertrophic subaortic stenosis).
• If sudden vision loss in one or both eyes occurs (NAION), discontinue therapy.
• If sudden hearing loss or tinnitus occurs, discontinue therapy.
• Priapism may occur, especially in patients with predisposing conditions (sickle cell anemia, multiple myeloma, leukemia).
• Not recommended in patients with retinitis pigmentosa.
• Alcohol may increase risk of orthostatic hypotension and cause dizziness, headache.

• Hypersensitivity to avanafil or any component
• Concomitant use with soluble guanylate cyclase (sGC) stimulators (e.g., riociguat) - can cause severe hypotension
• Concomitant use with nitrates or nitric oxide donors
• Severe hepatic or renal impairment (CrCl <30 mL/min)

• CYP3A4 Inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin): May increase avanafil levels; with moderate inhibitors, dose should not exceed 50 mg/24hr.
• Alpha-blockers (doxazosin, tamsulosin): May increase hypotensive effects; start with 50 mg dose.
• Antihypertensives: Additive hypotensive effects may occur.
• Nitrates: Severe hypotension risk; concomitant use is contraindicated.
• Alcohol: May increase risk of orthostatic hypotension.

May be taken with or without food. High-fat meals do not significantly affect absorption.

Pregnancy Category C: Avanafil is not indicated for use in pregnant women. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies the potential risk to the fetus.

Lactation: It is unknown if avanafil is excreted in human milk. Safety and efficacy have not been established in nursing mothers. Use with caution.

Safety and efficacy in pediatric patients (under 18 years) have not been established.

No dose adjustment needed for elderly patients (≥65 years), but higher sensitivity may occur.

Mild-moderate renal impairment (CrCl ≥30 mL/min): No dose adjustment needed.

Severe renal impairment (CrCl 15-29 mL/min): Do not use (safety and efficacy not established).

Mild-moderate hepatic impairment: No dose adjustment needed.

Severe hepatic impairment: Do not use.

Clinical data on avanafil overdose is limited. Overdose may cause headache, flushing, nasal congestion, dizziness, hypotension, priapism. Treatment: Symptomatic and supportive measures. No specific antidote.

Store below 30°C, in a cool and dry place, away from light. Keep out of reach of children.

Avanafil (C₂₃H₂₆ClN₇O₃)