Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
AVANAFIL vs ADCIRCA
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Selective inhibitor of phosphodiesterase type 5 (PDE5), enhancing nitric oxide-mediated relaxation of smooth muscle in the corpus cavernosum, increasing c GMP levels, and promoting penile erection.
Phosphodiesterase-5 (PDE5) inhibitor; increases c GMP in pulmonary vascular smooth muscle, leading to vasodilation.
Treatment of erectile dysfunction (FDA-approved),Pulmonary arterial hypertension (off-label)
Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise capacity and delay clinical worsening.,Off-label: Erectile dysfunction (not FDA-approved for this indication in the context of PAH).
100 mg orally once daily, taken 30-60 minutes before sexual activity. Maximum dosing frequency: once daily.
10 mg orally three times daily.
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.
Terminal half-life: 10–15 hours in healthy adults; prolonged in hepatic impairment (Child-Pugh B/C: up to 30 hours); clinical context: supports twice-daily dosing
Primarily metabolized by CYP3A4, with minor contributions from CYP2C9 and CYP2C19. Subject to first-pass metabolism.
Primarily metabolized by CYP3A4 (major) and CYP2C9 (minor) hepatic enzymes.
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).
Renal: ~70% (metabolites and unchanged drug), Fecal: ~20%, Biliary: minor
Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
96% bound to albumin and alpha-1-acid glycoprotein
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.
Vd: 0.4–0.7 L/kg; suggests distribution into total body water and moderate tissue binding
Oral bioavailability approximately 15-20% due to extensive first-pass metabolism. Absolute bioavailability not determined in humans; based on animal data.
Oral: 80%; absolute bioavailability: 50% due to first-pass metabolism
No dosage adjustment required for mild to moderate renal impairment (Cr Cl ≥30 m L/min). Not recommended for severe renal impairment (Cr Cl <30 m L/min) as safety and efficacy have not been established.
No dose adjustment required for mild to moderate renal impairment; avoid use in severe impairment (Cr Cl <30 m L/min) due to lack of data.
Child-Pugh Class A and B: No dosage adjustment required. Child-Pugh Class C: Not recommended due to lack of data.
Mild to moderate hepatic impairment (Child-Pugh A or B): 10 mg orally once daily; severe hepatic impairment (Child-Pugh C): contraindicated.
Not indicated for use in pediatric patients (age <18 years). Safety and efficacy not established.
Not established for patients <18 years.
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.
No specific dose adjustment, but caution due to increased sensitivity; monitor renal function.
None.
Do not use in patients taking nitrates (regularly or intermittently) due to risk of severe hypotension.
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.
Risk of hypotension, especially with nitrates or alpha-blockers.,Hematologic effects: increased risk of bleeding due to antiplatelet activity; caution with bleeding disorders or anticoagulants.,Vision loss: non-arteritic anterior ischemic optic neuropathy (NAION) has been reported; discontinue if sudden vision loss occurs.,Hearing loss: sudden decrease or loss of hearing; may be accompanied by tinnitus or dizziness.,Use caution in patients with left ventricular outflow obstruction (e.g., aortic stenosis) or severely impaired autonomic control of blood pressure.,Dose adjustment required with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir).
Concomitant use of organic nitrates (e.g., nitroglycerin, isosorbide mononitrate/dinitrate),Concomitant use of guanylate cyclase stimulators (e.g., riociguat),Hypersensitivity to avanafil or any component of the formulation,Severe hepatic impairment (Child-Pugh class C),Recent stroke or myocardial infarction (within 6 months),Patients with hypotension (BP <90/50 mm Hg)
Concomitant use of nitrates (any form) or nitric oxide donors.,Concomitant use with riociguat or other guanylate cyclase stimulators.,Known hypersensitivity to tadalafil or any component of the product.,Severe hepatic impairment (Child-Pugh class C).
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.
Avoid grapefruit and grapefruit juice as they may increase tadalafil levels and risk of side effects. No other significant food interactions. High-fat meals may delay absorption but do not require dose adjustment.
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.
Pregnancy Category B. Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. First trimester: risk cannot be ruled out; use only if clearly needed. Second and third trimesters: no known fetal risks, but caution advised due to maternal hypotension risk.
Not known if excreted in human milk. No data on M/P ratio. Caution advised; consider developmental benefits of breastfeeding vs potential adverse effects.
Not recommended. Excretion in human milk unknown. M/P ratio not established. Risk of hypotension in neonate. Alternative feeding method advised during therapy and for 48 hours after last dose.
No specific dose adjustments established; use lowest effective dose if indicated. Pharmacokinetic changes in pregnancy unknown; monitor for efficacy and adverse effects.
No specific pharmacokinetic data in pregnancy. Standard dose (40 mg orally once daily) recommended. Monitor for hypotension; dose adjustment not routinely required unless maternal hypotension develops.
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.
Adcirca (tadalafil) is a PDE5 inhibitor indicated for pulmonary arterial hypertension (PAH) to improve exercise ability. It is dosed at 40 mg once daily, not as needed. Avoid use with nitrates due to risk of severe hypotension. Monitor for vision loss (non-arteritic anterior ischemic optic neuropathy) and hearing loss. Use caution in patients with hepatic impairment (Child-Pugh class B: reduce dose; class C: contraindicated). Dose adjustment required with potent CYP3A4 inhibitors (e.g., ketoconazole: reduce to 20 mg). Not recommended for severe renal impairment (Cr Cl <30 m L/min) or on hemodialysis.
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.
Take Adcirca exactly as prescribed, 40 mg once daily, at the same time each day. Do not take it as needed for erectile dysfunction.,Do not take Adcirca if you are taking any form of nitrate medication (e.g., nitroglycerin) or recreational drugs called 'poppers' (amyl nitrate) as this can cause a sudden dangerous drop in blood pressure.,Seek immediate medical attention if you experience sudden vision loss or decrease in hearing, as these may be signs of a serious side effect.,Avoid drinking large amounts of alcohol (e.g., 3 or more drinks) within a short time while taking Adcirca, as it may increase the risk of dizziness, lightheadedness, and fainting.,Inform your healthcare provider about all medications you take, including prescription, over-the-counter, and herbal products, especially alpha-blockers, erythromycin, or ritonavir.,Adcirca may cause dizziness. Do not drive or operate machinery until you know how the medicine affects you.
"Avanafil, a phosphodiesterase type 5 (PDE5) inhibitor, enhances the vasodilatory effects of nitric oxide by increasing cyclic guanosine monophosphate (cGMP) levels. Acebutolol, a cardioselective beta-blocker, reduces cardiac output and sympathetic outflow. Concurrent use may lead to additive hypotension, particularly during initiation or dose escalation, potentially causing dizziness, syncope, or orthostatic hypotension."
"Cobicistat is a potent inhibitor of CYP3A4, the primary enzyme responsible for metabolizing avanafil. Co-administration significantly increases avanafil's systemic exposure, potentially doubling its plasma concentration and half-life. This elevated exposure raises the risk of avanafil-associated adverse effects, such as hypotension, priapism, and visual disturbances, and may also enhance cobicistat's own serum levels due to shared metabolic pathways, increasing the likelihood of nephrotoxicity and other protease inhibitor-related toxicities."
"Isavuconazonium is a prodrug of isavuconazole, a triazole antifungal that inhibits CYP3A4 and CYP3A5. Coadministration with avanafil, a PDE5 inhibitor metabolized primarily by CYP3A4, can increase avanafil exposure due to reduced clearance. This may elevate the risk of avanafil-associated adverse effects such as hypotension, priapism, and visual disturbances."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about AVANAFIL vs ADCIRCA, answered by our medical review team.
AVANAFIL is a PDE5 Inhibitor that works by Selective inhibitor of phosphodiesterase type 5 (PDE5), enhancing nitric oxide-mediated relaxation of smooth muscle in the corpus cavernosum, increasing c GMP levels, and promoting penile erection.. ADCIRCA is a PDE5 Inhibitor that works by Phosphodiesterase-5 (PDE5) inhibitor; increases c GMP in pulmonary vascular smooth muscle, leading to vasodilation.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between AVANAFIL and ADCIRCA depend on the specific clinical indication. These are both PDE5 Inhibitor agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of AVANAFIL is: 100 mg orally once daily, taken 30-60 minutes before sexual activity. Maximum dosing frequency: once daily.. The standard adult dose of ADCIRCA is: 10 mg orally three times daily.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between AVANAFIL and ADCIRCA in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. AVANAFIL is classified as Category C. 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 onl. ADCIRCA is classified as Category C. Pregnancy Category B. Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. First trimester: risk cannot be rule. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.