AVANAFIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVANAFIL (AVANAFIL).
Selective inhibitor of phosphodiesterase type 5 (PDE5), enhancing nitric oxide-mediated relaxation of smooth muscle in the corpus cavernosum, increasing cGMP levels, and promoting penile erection.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP2C9 and CYP2C19. Subject to first-pass metabolism. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP2C9, with metabolites excreted in feces (approximately 82-90%) and urine (approximately 6-8% as unchanged drug and minor metabolites). |
| Half-life | Terminal elimination half-life approximately 6-8 hours. Clinical context: Supports once-daily dosing; steady-state reached within 5 days with no accumulation at FDA-approved dose. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution approximately 200 L (≈ 2.9 L/kg for a 70 kg individual). Clinical meaning: Indicates extensive tissue distribution, with high affinity for genital tissues. |
| Bioavailability | Oral bioavailability approximately 15-20% due to extensive first-pass metabolism. Absolute bioavailability not determined in humans; based on animal data. |
| Onset of Action | Oral administration: Rapid absorption with clinical effect (erection sufficient for intercourse) achieved as early as 30 minutes, with maximum effect at approximately 1-2 hours. |
| Duration of Action | Duration of effect up to 6-8 hours. Clinical notes: Erectile response may occur up to 12 hours post-dose; food does not significantly affect AUC but may delay Tmax. |
| Molecular Weight | 483.57 |
100 mg orally once daily, taken 30-60 minutes before sexual activity. Maximum dosing frequency: once daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) as safety and efficacy have not been established. |
| Liver impairment | Child-Pugh Class A and B: No dosage adjustment required. Child-Pugh Class C: Not recommended due to lack of data. |
| Pediatric use | Not indicated for use in pediatric patients (age <18 years). Safety and efficacy not established. |
| Geriatric use | No dosage adjustment required solely based on age. However, consider lower starting dose (50 mg) in patients ≥65 years due to potential increased sensitivity and decreased clearance. |
| 1st trimester | No adequate human data; animal studies suggest risk. Avoid use in first trimester unless clearly needed. |
| 2nd trimester | No adequate human data; potential risk to fetus. Use only if benefit outweighs risk. |
| 3rd trimester | No adequate human data; potential for uterine relaxation and hypotension. Avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for AVANAFIL (AVANAFIL).
| Placental transfer | Crosses placenta in animal studies; human data unavailable. Likely to cross due to molecular weight and lipophilicity. |
| Breastfeeding | Excretion into human milk unknown; significant potential for adverse effects in infant. Use caution; consider alternative therapy or temporary cessation of breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Concurrent nitrates in any formHypersensitivity to avanafil or any componentConcurrent use of guanylate cyclase stimulators (e.g., riociguat)Severe hepatic impairment (Child-Pugh class C)
| Precautions | Cardiovascular risk: Not recommended in patients with unstable angina, recent MI (within 90 days), or uncontrolled arrhythmias., Hypotension: Caution with alpha-blockers or antihypertensives; avoid in those with hypotension (BP <90/50 mm Hg)., Priapism: Advise patients to seek immediate medical attention for erections lasting >4 hours., Hepatic impairment: Avoid use in severe hepatic impairment (Child-Pugh class C)., Renal impairment: Not recommended in patients on renal dialysis., Visual effects: Non-arteritic anterior ischemic optic neuropathy (NAION) reported, though rare. |
| Food/Dietary | Avanafil can be taken with or without food. However, a high-fat meal may delay absorption and reduce peak plasma concentration, potentially prolonging time to onset. Grapefruit juice may increase avanafil levels; avoid concurrent consumption. |
Loading safety data…
| L3 (Moderately Safe) - Limited data; potential risk. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. Animal studies show no evidence of teratogenicity at exposures up to 18 times the MRHD. Risk cannot be ruled out; use only if clearly needed. |
| Fetal Monitoring | Monitor for hypotension, priapism, and visual disturbances. No specific fetal monitoring required beyond standard prenatal care. |
| Fertility Effects | Reversible impairment of spermatogenesis and fertility observed in animal studies. Human data insufficient; potential for reduced male fertility. |
| Clinical Pearls | Avanafil is a rapid-onset PDE5 inhibitor with a Tmax of 30-45 minutes, making it suitable for on-demand use. It has minimal interaction with alpha-blockers compared to other PDE5 inhibitors, but caution is still advised. Avoid use in patients taking nitrates or those with severe hepatic impairment (Child-Pugh C). Its short half-life (5 hours) reduces the duration of side effects like headache and flushing. |
| Patient Advice | Take avanafil approximately 30 minutes before sexual activity, with or without food. · Do not take more than one dose in a 24-hour period. · Seek emergency medical attention if you experience an erection lasting more than 4 hours (priapism) or sudden vision loss. · Avoid alcohol or limit to small amounts as it may increase side effects like dizziness or hypotension. · Inform your doctor if you are taking any medications, especially nitrates, alpha-blockers, or antihypertensives. |