Skip to Content

Avanafil

Medically reviewed by Drugs.com. Last updated on May 24, 2020.

Pronunciation

(a VAN a fil)

Index Terms

  • Stendra

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Stendra: 50 mg, 100 mg, 200 mg

Brand Names: U.S.

  • Stendra

Pharmacologic Category

  • Phosphodiesterase-5 Enzyme Inhibitor

Pharmacology

Does not directly cause penile erections, but affects the response to sexual stimulation. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation and inflow of blood to the corpus cavernosum. Avanafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE-5), which is responsible for degradation of cGMP in the corpus cavernosum; when sexual stimulation causes local release of NO, inhibition of PDE-5 by avanafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum; at recommended doses, it has no effect in the absence of sexual stimulation.

Absorption

Rapid

Metabolism

Hepatic via CYP3A4 (major), CYP2C (minor); forms metabolites (active and inactive)

Excretion

Feces (~62%); urine (~21%)

Time to Peak

Plasma: 30 to 45 minutes (fasting); 1.12 to 1.25 hours (high-fat meal)

Half-Life Elimination

Terminal: ~5 hours

Protein Binding

~99%

Special Populations: Renal Function Impairment

In mild renal impairment, AUC0-inf decreased by 2.9%and Cmax increased by 2.8%; in moderate renal impairment, AUC0-inf increased by 9.1% and Cmax decreased by 2.8%.

Special Populations: Hepatic Function Impairment

In mild hepatic impairment, AUC0-inf increased by 3.8% and Cmax decreased by 2.7%; in moderate hepatic impairment, AUC0-inf increased by 11.2% and Cmax decreased by 51%.

Special Populations: Elderly

AUC0-inf increased by 6.8% and Cmax decreased by 2.1%.

Use: Labeled Indications

Erectile dysfunction: Treatment of erectile dysfunction

Contraindications

Hypersensitivity to avanafil or any component of the formulation; coadministration with any form of organic nitrates (either regularly and/or intermittently) or guanylate cyclase stimulators (eg, riociguat)

Dosing: Adult

Erectile dysfunction: Oral: Initial: 100 mg (or 50 mg if concurrently receiving an alpha blocker) taken ~15 minutes prior to sexual activity; taken as one single dose and not more than once daily; dose may be increased to 200 mg ~15 minutes prior to sexual activity or decreased to 50 mg ~30 minutes prior to sexual activity using the lowest dose that provides benefit; maximum 200 mg daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Elderly ≥65 years: Refer to adult dosing.

Administration

May be administered with or without food, ~15 to 30 minutes prior to sexual activity.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted to 30°C (86°F). Protect from light.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Alcohol (Ethyl): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Monitor therapy

Alpha1-Blockers (Nonselective): Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Alpha1-Blockers (Nonselective). Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Consider therapy modification

Alpha1-Blockers (Uroselective): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Monitor therapy

Alprostadil: Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil. Avoid combination

Amyl Nitrite: Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Amyl Nitrite. Avoid combination

Blood Pressure Lowering Agents: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Avanafil. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Avanafil. Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Avanafil. Management: The maximum avanafil dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects (eg, hypotension, syncope, priapism). Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Avanafil. Avoid combination

Dapoxetine: May enhance the orthostatic hypotensive effect of Phosphodiesterase 5 Inhibitors. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lorcaserin (Withdrawn From US Market): May enhance the adverse/toxic effect of Phosphodiesterase 5 Inhibitors. Specifically, the risk of developing priapism may be increased. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Avoid combination

Nitroprusside: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Nitroprusside. Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the adverse/toxic effect of other Phosphodiesterase 5 Inhibitors. Avoid combination

Riociguat: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Riociguat. Avoid combination

Sapropterin: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Simeprevir: May increase the serum concentration of Phosphodiesterase 5 Inhibitors. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Vasodilators (Organic Nitrates): Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Avoid combination

Adverse Reactions

>10%: Central nervous system: Headache (1% to 12%)

2% to 10%:

Cardiovascular: Flushing (3% to 10%), ECG abnormality (1% to 3%)

Central nervous system: Dizziness (1% to 2%)

Gastrointestinal: Viral gastroenteritis (≤2%)

Neuromuscular & skeletal: Back pain (1% to 3%)

Respiratory: Nasopharyngitis (1% to 5%), nasal congestion (1% to 3%), upper respiratory tract infection (1% to 3%)

<2%, postmarketing, and/or case reports: Abdominal distress, angina pectoris, anterior ischemic optic neuropathy (nonarteritic), arthralgia, balanitis, bronchitis, constipation, cough, deep vein thrombosis, depression, diarrhea, drowsiness, dyspepsia, dyspnea on exertion, epistaxis, fatigue, gastritis, gastroesophageal reflux disease, hearing loss, hematuria, hyperglycemia, hypertension, hypoglycemia, hypotension, increased serum ALT, influenza, insomnia, limb pain, muscle spasm, musculoskeletal pain, myalgia, nausea, nephrolithiasis, oropharyngeal pain, palpitations, peripheral edema, pollakiuria, priapism, pruritus, sinus congestion, sinusitis, skin rash, tinnitus, urinary tract infection, vertigo, vision color changes, vision loss (temporary or permanent), vomiting, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Color discrimination: May cause dose-related impairment of color discrimination. Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterases (no safety information available).

• Hearing loss: Sudden decrease or loss of hearing has been reported rarely; hearing changes may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined.

• Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis or hypertrophic obstructive cardiomyopathy); may be more sensitive to hypotensive actions. Concurrent use with alpha-adrenergic antagonist therapy may cause symptomatic hypotension; patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose. Patients should avoid or limit concurrent substantial ethanol consumption as this may increase the risk of symptomatic hypotension.

• Priapism: Painful erection >6 hours in duration has been reported (rarely). Instruct patients to seek immediate medical attention if erection persists >4 hours. Use with caution in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia).

• Vision loss: Vision loss may occur rarely and be a sign of nonarteritic anterior ischemic optic neuropathy (NAION). Instruct patients to seek medical assistance for sudden loss of vision in one or both eyes. Patients who have already experienced NAION are at an increased risk of recurrence. Other risk factors for NAION include low cup-to-disc ratio (“crowded disc”), coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and >50 years of age. Use with caution in these patients only when the benefits outweigh the risks. Safety and efficacy were not studied in patients with known degenerative retinal disorders (eg, retinitis pigmentosa); use is not recommended.

Disease-related concerns:

• Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease).

• Bleeding disorders: Use with caution in patients with bleeding disorders; safety and efficacy have not been established.

• Cardiovascular disease: Use is not recommended in patients with hypotension (<90/50 mm Hg); uncontrolled hypertension (>170/100 mm Hg); unstable angina or angina during intercourse; life-threatening arrhythmias, stroke, MI, or coronary revascularization within the last 6 months; cardiac failure or coronary artery disease causing unstable angina. Safety and efficacy have not been studied in these patients. Use caution in patients with left ventricular outflow obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy with outflow tract obstruction). There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction.

• Hepatic impairment: Safety and efficacy have not been studied in patients with severe hepatic impairment (Child-Pugh class C); therefore, use in these patients is not recommended.

• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; safety and efficacy have not been established.

• Renal impairment: Safety and efficacy have not been studied in patients with severe renal impairment or end-stage renal disease requiring dialysis, therefore, use in these patients is not recommended.

Concurrent drug therapy issues:

• Nitrates: Use of avanafil is contraindicated in patients currently taking nitrate preparations. According to the manufacturer, when nitrate administration is deemed medically necessary in a life-threatening situation, may administer nitrates only if 12 hours has elapsed after avanafil use. Of note, the elimination half-life of avanafil is similar to that of sildenafil and vardenafil which both require 24 hours to elapse prior to administration of nitrates (ACCF/AHA [Anderson, 2013]; ACCF/AHA [O'Gara, 2013]).

Other warnings/precautions:

• Appropriate use: Potential underlying causes of erectile dysfunction should be evaluated prior to treatment.

Monitoring Parameters

Monitor for response, adverse reactions, blood pressure, and heart rate.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. This product is not indicated for use in females.

Patient Education

What is this drug used for?

• It is used to treat erectile dysfunction (ED).

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Flushing

• Sore throat

• Back pain

• Stuffy nose

• Runny nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Severe dizziness

• Passing out

• Severe headache

• Severe nausea

• Severe vomiting

• Vision changes

• Eye pain

• Severe eye irritation

• Blindness

• Trouble hearing

• Noise or ringing in the ears

• Erection that lasts more than 4 hours

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.