Avanafil

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 cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.

• Avanafil tablets are a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction in adult males.ICD-10: N52.9

• • Administration of avanafil tablet to patients using any form of organic nitrate is contraindicated ( 4.1 ) • Hypersensitivity to any component of the avanafil tablet ( 4.2 ) • Administration with guanylate cyclase (GC) stimulators such as riociguat and vericiguat ( 4.3 ) 4.1 Nitrates Administration of avanafil tablets with any form of organic nitrates, either regularly and/or intermittently, is contraindicated. Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, avanafil has been shown to potentiate the hypotensive effects of nitrates.contraindicated

• The starting dose is 100 mg taken as early as approximately 15 minutes before sexual activity, on an as needed basis ( 2.1 ) • Take avanafil tablet no more than once a day ( 2.1 ). • Based on efficacy and/or tolerability, the dose may be increased to 200 mg taken as early as approximately 15 minutes before sexual activity or decreased to 50 mg taken approximately 30 minutes before sexual activity. Use the lowest dose that provides benefit ( 2.1 ). • Avanafil tablet may be taken with or without food ( 2.2 ) • Do not use avanafil tablet with strong CYP3A4 inhibitors ( 2.3 ) • If taking a moderate CYP3A4 inhibitor, the dose should be no more than 50 mg in a 24-hour period ( 2.3 ). • In patients on stable alpha-blocker therapy, the recommended starting dose of avanafil tablet is 50 mg ( 2.3 ). 2.1 Erectile Dysfunction The recommended starting dose is 100 mg. Avanafil tablets should be taken orally as needed as early as approximately 15 minutes before sexual activity. Based on individual efficacy and tolerability, the dose may be increased to 200 mg taken as early as approximately 15 minutes before sexual activity, or decreased to 50 mg taken approximately 30 minutes before sexual activity. The lowest dose that provides benefit should be used. The maximum recommended dosing frequency is once per day. Sexual stimulation is required for a response to treatment. 2.2 Use with Food Avanafil tablets may be taken with or without food. 2.3 Concomitant Medications Nitrates Concomitant use of nitrates in any form is contraindicated [see Contraindications ( 4.1 )].

Evaluation of erectile dysfunction (ED) should include an appropriate medical assessment to identify potential underlying causes, as well as treatment options. Before prescribing avanafil, it is important to note the following: • Patients should not use avanafil if sexual activity is inadvisable due to cardiovascular status or any other reason ( 5.1 ) • Use of avanafil with alpha-blockers, other antihypertensives, or substantial amounts of alcohol (greater than 3 units) may lead to hypotension ( 2.3 , 5.6 , 5.7 ) • Patients should seek emergency treatment if an erection lasts greater than 4 hours ( 5.3 ) • Patients should stop avanafil and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non Arteritic Ischemic Optic Neuropathy (NAION). Avanafil should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a “crowded” optic disc may also be at an increased risk of NAION ( 5.4 , 6.2 ) • Patients should stop taking avanafil and seek prompt medical attention in the event of sudden decrease or loss of hearing ( 5.5 ) 5.1 Cardiovascular Risk There is a potential for cardiac risk during sexual activity in patients with pre-existing cardiovascular disease. Therefore, treatments for ED, including avanafil, should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.

Most common adverse reactions (greater than or equal to 2%) include headache, flushing, nasal congestion, nasopharyngitis, and back pain ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Avanafil was administered to 2215 men during clinical trials. In trials of avanafil for use as needed, a total of 493 patients were exposed for greater than or equal to 6 months, and 153 patients were treated for greater than or equal to 12 months. In three randomized, double-blind, placebo-controlled trials lasting up to 3 months in duration, the mean age of patients was 56.4 years (range from 23 to 88 years). 83.9% of patients were White, 13.8% were Black, 1.4% Asian, and <1% Hispanic. 41.1% were current or previous smokers. 30.6% had diabetes mellitus. The discontinuation rate due to adverse reactions for patients treated with avanafil 50 mg, 100 mg, or 200 mg was 1.4%, 2.0%, and 2.0%, respectively, compared to 1.7% for placebo-treated patients. Table 1 presents the adverse reactions reported when avanafil was taken as recommended (on an as-needed basis) from these 3 clinical trials.

• Do not use in patients with severe renal impairment ( 8.6 ) • Do not use in patients with severe hepatic impairment ( 8.7 ) 8.1 Pregnancy Risk Summary Avanafil is not indicated for use in females. There are no data with the use of avanafil in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In animal reproduction studies conducted in pregnant rats and rabbits, no adverse developmental outcomes were observed with oral administration of avanafil during organogenesis at exposures for total avanafil at approximately 8 and 6 times, respectively, the Maximum Recommended Human Dose (MRHD) of 200 mg based on AUC (see Data). Data Animal Data In pregnant rats administered orally at 100, 300, or 1000 mg/kg/day from gestation days 6 to 17, no evidence of teratogenicity, embryotoxicity, or fetotoxicity was observed at up to 300 mg/kg/day. This dose is equivalent to exposures of approximately 8 times the exposure at the Maximum Recommended Human Dose (MRHD) of 200 mg based on AUCs for total avanafil. At the maternally toxic dose (1000 mg/kg/day), decreased fetal body weight occurred with no signs of teratogenicity. In pregnant rabbits administered orally at 30, 60, 120, or 240 mg/kg/day from gestation days 6 to 18, no teratogenicity was observed at exposures up to approximately 6 times the human exposure at the MRHD based on AUCs for total avanafil.

Metabolism

Mean avanafil plasma concentrations measured after the administration of a single oral dose of 50 or 200 mg to healthy male volunteers are depicted in Figure 4. The pharmacokinetics of avanafil are dose proportional from 12.5 to 600 mg.

Single doses up to 800 mg have been given to healthy subjects, and multiple doses up to 300 mg have been given to patients. In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance because avanafil is highly bound to plasma proteins and is not significantly eliminated in the urine.

• Jun 14, 2024ANDAANDA209266Hetero Labs Ltd V

1. 1Eye Inflammation1219%
2. 2Bladder Cancer1016%
3. 3Paraesthesia711%
4. 4Drug Ineffective57.8%
5. 5Acute Kidney Injury34.7%
6. 6Circulatory Collapse34.7%
7. 7Fatigue34.7%
8. 8Optic Ischaemic Neuropathy34.7%
9. 9Retinal Vascular Occlusion34.7%
10. 10Serous Retinal Detachment34.7%
11. 11Abdominal Pain23.1%
12. 12Agitation23.1%
13. 13Back Pain23.1%
14. 14Diarrhoea23.1%
15. 15Headache23.1%

The 10 most recently updated of 24 ClinicalTrials.gov registrations naming Avanafil as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Daily Avanafil for Erectile Dysfunction
  Completed · Phase 4 · Interventional · 70 enrolled · University of Alexandria
  NCT04374994updated 2020-09-16
• Avanafil Versus Sildenafil in Spinal Cord Injury Erectile Dysfunction
  Unknown · Phase 4 · Interventional · 78 enrolled · Eduardo Vargas-Baquero
  NCT03169582updated 2017-05-30
• This Study is to Evaluate the Safety and Efficacy of Avanafil in the Treatment of Erectile Dysfunction.
  Completed · Phase 3 · Interventional · 195 enrolled · JW Pharmaceutical
  NCT01705197updated 2017-03-10
• Efficacy and Tolerability Study of Avanafil in Russia
  Completed · Phase 3 · Interventional · 189 enrolled · Sanofi
  NCT02503306updated 2016-03-17
• Study Evaluating the Effects of Avanafil on Semen Parameters
  Completed · Phase 4 · Interventional · 181 enrolled · VIVUS LLC
  NCT01768676updated 2015-12-14
• Efficacy and Safety of Avanafil in the Patients With Erectile Dysfunction
  Completed · Phase 2 · Interventional · 159 enrolled · Pusan National University Hospital
  NCT02477436updated 2015-06-24
• Safety Study Looking at the Effects of Stendra on Vision
  Completed · Phase 4 · Interventional · 80 enrolled · VIVUS LLC
  NCT02033200updated 2015-03-13
• Research Evaluating a PDE5 Inhibitor for Erectile Dysfunction
  Completed · Phase 4 · Interventional · 440 enrolled · VIVUS LLC
  NCT01698684updated 2014-10-27
• Research Evaluating an Investigational Medication for Erectile Dysfunction - Post-Prostatectomy
  Completed · Phase 3 · Interventional · 298 enrolled · VIVUS LLC
  NCT00895011updated 2012-10-01
• Long-Term Safety and Efficacy Study of Avanafil in Men With Erectile Dysfunction
  Completed · Phase 3 · Interventional · 712 enrolled · VIVUS LLC
  NCT00853606updated 2012-08-17

Frequently asked questions

How does Avanafil work?

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 cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.

What is Avanafil used for?

According to FDA labeling, Avanafil carries indications including: Avanafil tablets are a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction in adult males.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Avanafil?

Avanafil is classified as Drugs used in erectile dysfunction, Phosphodiesterase 5 Inhibitor, Guanylate Cyclase Stimulators, Phosphodiesterase 5 Inhibitors, Enhance Penile Erection, Penile Venous Vasodilation.

What are the brand names for Avanafil?

Avanafil is marketed under brand names including Stendra.

What are the contraindications for Avanafil?

Avanafil labeling lists contraindications including: • Administration of avanafil tablet to patients using any form of organic nitrate is contraindicated ( 4.1 ) • Hypersensitivity to any component of the avanafil tablet ( 4.2 ) • Administration with guanylate cyclase (GC) stimulators such as riociguat and vericiguat ( 4.3 ) 4.1 Nitrates Administration of avanafil tablets with any form of organic nitrates, either regularly and/or intermittently, is contraindicated. Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, avanafil has been shown to potentiate the hypotensive effects of nitrates.. Always consult the full prescribing information and a clinician.