Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
CIALIS vs AVANAFIL
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Phosphodiesterase-5 (PDE5) inhibitor; increases c GMP levels, causing smooth muscle relaxation and vasodilation in the corpus cavernosum, enhancing erectile function.
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.
Treatment of erectile dysfunction,Treatment of benign prostatic hyperplasia,Treatment of pulmonary arterial hypertension (as Adcirca)
Treatment of erectile dysfunction (FDA-approved),Pulmonary arterial hypertension (off-label)
Tadalafil 10 mg or 20 mg orally as needed at least 30 minutes before sexual activity; maximum dosing frequency once daily. Alternative: 2.5 mg or 5 mg once daily for daily use.
100 mg orally once daily, taken 30-60 minutes before sexual activity. Maximum dosing frequency: once daily.
The terminal elimination half-life of tadalafil is approximately 17.5 hours in healthy subjects, which supports once-daily dosing for erectile dysfunction and once-daily use for benign prostatic hyperplasia. This long half-life distinguishes it from other PDE5 inhibitors.
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.
Primarily hepatic via CYP3A4; minor pathways include CYP2C9 and glucuronidation.
Primarily metabolized by CYP3A4, with minor contributions from CYP2C9 and CYP2C19. Subject to first-pass metabolism.
Following oral administration, tadalafil is predominantly eliminated by hepatic metabolism. The metabolites are excreted mainly in feces (approximately 61% of the dose) and to a lesser extent in urine (approximately 36% of the dose). No unchanged parent drug is detected in urine.
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).
Tadalafil is 94% bound to plasma proteins, primarily to albumin. The protein binding is independent of drug concentration over a wide range.
Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
The apparent volume of distribution (Vd/F) is approximately 63 L (or roughly 0.9 L/kg for a 70 kg individual), indicating distribution into tissues beyond the vascular space, including the penis and other target organs.
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.
Absolute oral bioavailability of tadalafil has not been formally determined; however, the drug is well absorbed after oral administration, with peak plasma concentrations reached in 0.5 to 6 hours (median 2 hours). Food does not affect the extent of absorption (AUC), though it may delay the rate (Tmax) by about 1–2 hours.
Oral bioavailability approximately 15-20% due to extensive first-pass metabolism. Absolute bioavailability not determined in humans; based on animal data.
Cr Cl 30-50 m L/min: 5 mg once daily (max) for daily use; as-needed dosing: 10 mg not to exceed once every 48 hours. Cr Cl <30 m L/min: not recommended. Hemodialysis: not studied.
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.
Child-Pugh A and B: no dose adjustment necessary for as-needed dosing; daily use: caution, start at 5 mg once daily. Child-Pugh C: not recommended.
Child-Pugh Class A and B: No dosage adjustment required. Child-Pugh Class C: Not recommended due to lack of data.
Not indicated for pediatric patients under 18 years.
Not indicated for use in pediatric patients (age <18 years). Safety and efficacy not established.
No dose adjustment required solely based on age; consider renal function and concomitant medications.
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.
None
None.
Risk of hypotension with vasodilators or alpha-blockers,Contraindicated with nitrates due to severe hypotension risk,Patients with left ventricular outflow obstruction (e.g., aortic stenosis) should avoid use,Caution in patients with hypotension, severe hepatic impairment, or end-stage renal disease,Risk of priapism: advise immediate medical attention for erections lasting >4 hours,Decreased visual or hearing ability requiring discontinuation
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.
Concomitant use of nitrates (any form) or riociguat,Hypersensitivity to tadalafil,Concomitant use with alpha-blockers (except for BPH with appropriate dosing)
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)
Avoid high-fat meals prior to dosing as they may delay absorption and reduce peak plasma concentration. Avoid large quantities of grapefruit juice (more than 1 liter per day) as it may increase tadalafil exposure via CYP3A4 inhibition.
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.
FDA Pregnancy Category B. Animal studies show no evidence of teratogenicity or embryotoxicity. No adequate, well-controlled studies in pregnant women. Risk cannot be ruled out; use only if clearly needed.
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.
Excretion in human milk unknown. Not recommended for use in nursing mothers. M/P ratio not determined.
Not known if excreted in human milk. No data on M/P ratio. Caution advised; consider developmental benefits of breastfeeding vs potential adverse effects.
No specific dose adjustments studied in pregnancy. Use lowest effective dose if necessary, with caution for increased plasma volume and renal clearance potentially altering pharmacokinetics.
No specific dose adjustments established; use lowest effective dose if indicated. Pharmacokinetic changes in pregnancy unknown; monitor for efficacy and adverse effects.
Tadalafil (Cialis) has a 17.5-hour half-life allowing once-daily dosing for ED or daily for BPH/LUTS. Avoid use with nitrates; may cause prolonged erection. Onset of action is 30-60 minutes, and effect may last up to 36 hours. Use with caution in patients with left ventricular outflow obstruction or severe hepatic impairment.
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.
Do not take tadalafil if you take any form of nitrate medication (e.g., nitroglycerin) for chest pain.,Seek immediate medical help if you have an erection lasting more than 4 hours.,Avoid alcohol consumption as it may increase the risk of dizziness and low blood pressure.,Take tadalafil at least 30 minutes before sexual activity; effect can last up to 36 hours.,For daily use, take at the same time each day without regard to timing of sexual activity.,Grapefruit and grapefruit juice may increase tadalafil levels; avoid large amounts.,Inform your doctor of all medications you take, especially alpha-blockers, antihypertensives, and antifungal or antibiotic drugs.
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.
No interactions on record
"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."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about CIALIS vs AVANAFIL, answered by our medical review team.
CIALIS is a PDE5 Inhibitor that works by Phosphodiesterase-5 (PDE5) inhibitor; increases c GMP levels, causing smooth muscle relaxation and vasodilation in the corpus cavernosum, enhancing erectile function.. 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.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between CIALIS and AVANAFIL 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 CIALIS is: Tadalafil 10 mg or 20 mg orally as needed at least 30 minutes before sexual activity; maximum dosing frequency once daily. Alternative: 2.5 mg or 5 mg once daily for daily use.. The standard adult dose of AVANAFIL is: 100 mg orally once daily, taken 30-60 minutes before sexual activity. Maximum dosing frequency: once 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 CIALIS and AVANAFIL 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. CIALIS is classified as Category C. FDA Pregnancy Category B. Animal studies show no evidence of teratogenicity or embryotoxicity. No adequate, well-controlled studies in pregnant women. Risk cannot be ruled out; use. 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. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.