Avanafil

Oral
Erectile dysfunction

Patients who are stable on α-blocker therapy: Initially, 50 mg as a single dose taken as needed approx 15-30 minutes before sexual activity.

Patients receiving moderate CYP3A4 inhibitors (e.g. erythromycin, fluconazole, diltiazem, verapamil, amprenavir, fosamprenavir, aprepitant): Max: 100 mg once 48 hourly or 50 mg once 24 hourly.

CrCl (mL/min)	Dosage
<30	Contraindicated.

Mild to moderate (Child-Pugh class A or B): Initiate with the lowest effective dose and adjust dose according to patient's tolerance. Severe (Child-Pugh class C): Contraindicated.

tab: May be taken with or without food. Avoid grapefruit juice.

Resting hypotension (blood pressure <90/50 mmHg), uncontrolled hypertension (blood pressure >170/100 mmHg), unstable angina, angina occurring during sexual intercourse, heart failure (NYHA class II or greater); stroke, MI, or life-threatening arrhythmia within the last 6 months; hereditary degenerative retinal disorders (e.g. retinitis pigmentosa), vision loss due to non-arteritic anterior ischaemic optic neuropathy (NAION). Severe renal (CrCl <30 mL/min) and hepatic (Child-Pugh class C) impairment. Concomitant use with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, telithromycin, nefazodone, ritonavir, nelfinavir, saquinavir), guanylate cyclase stimulators (e.g. riociguat, vericiguat), and any form of organic nitrates.

Patient with anatomical penis deformation (e.g. angulation, cavernosal fibrosis, Peyronie's disease); predisposition to priapism (e.g. sickle cell anaemia, multiple myeloma, leukaemia), bleeding disorder; active peptic ulcer disease; left ventricular outflow obstruction (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy). Patients receiving α-blockers or moderate CYP3A4 inhibitors. Not indicated for use in women. Not recommended for use in patients who had coronary revascularisation within the last 6 months. Mild to moderate hepatic impairment (Child-Pugh class A or B).

Significant: May cause impaired colour discrimination (dose-related); hypotension, hypersensitivity reactions (e.g. pruritus, eyelid swelling). Rarely, sudden decrease or loss of hearing (may be accompanied by tinnitus and dizziness); priapism, vision loss, NAION.
Cardiac disorders: Palpitations.
Eye disorders: Blurred vision.
Gastrointestinal disorders: Nausea, vomiting, stomach discomfort, dyspepsia.
General disorders and administration site conditions: Fatigue.
Investigations: Abnormal ECG, increased heart rate, increased hepatic enzyme.
Musculoskeletal and connective tissue disorders: Back pain, muscle tightness.
Nervous system disorders: Headache, dizziness, somnolence, sinus headache.
Respiratory, thoracic and mediastinal disorders: Nasal or sinus congestion, nasopharyngitis, exertional dyspnoea.
Vascular disorders: Flushing.

Physical examination and medical history must be undertaken to diagnose erectile dysfunction and identify possible underlying causes and appropriate treatment options. Assess CV status prior to treatment. Monitor blood pressure, heart rate, adverse reactions and for response or efficacy.

Enhanced hypotensive effect with α-blockers (e.g. doxazosin, tamsulosin) or other antihypertensive agents (e.g. amlodipine, enalapril). Increased exposure with moderate CYP3A4 inhibitors (e.g. erythromycin, fluconazole, diltiazem, verapamil, amprenavir, fosamprenavir, aprepitant).
Potentially Fatal: Additive hypotensive effect with any form of organic nitrates and guanylate cyclase stimulators (e.g. riociguat, vericiguat). Increased exposure with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, telithromycin, nefazodone, ritonavir, nelfinavir, saquinavir).

Increased hypotensive effect with alcohol. May increase exposure with grapefruit juice.

Description:
Mechanism of Action: Avanafil is a highly selective inhibitor of phosphodiesterase type 5 (PDE5). During sexual stimulation, avanafil enhances the effect of nitric oxide by inhibiting PDE5 causing increased levels of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the penis. This produces smooth muscle relaxation and inflow of blood into the penile tissue, thereby causing an erection. It has no effect in the absence of sexual stimulation.
Pharmacokinetics:
Absorption: Rapidly absorbed. Time to peak plasma concentration: 30-45 minutes (fasted state); 1.12-1.25 hours (with high-fat meal).
Distribution: Plasma protein binding: Approx 99%.
Metabolism: Metabolised in the liver mainly by CYP3A4 isoenzyme and to a minor extent by CYP2C isoform into M4 (active) and M16 (inactive) metabolites.
Excretion: Mainly via faeces (approx 62%); urine (approx 21%). Terminal elimination half-life: Approx 5-17 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 9869929, Avanafil. https://pubchem.ncbi.nlm.nih.gov/compound/Avanafil. Accessed Nov. 22, 2023.

Store below 30°C. Protect from light.

Drugs for Erectile Dysfunction & Ejaculatory Disorders

G04BE10 - avanafil ; Belongs to the class of drugs used in erectile dysfunction.

Anon. Avanafil. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 05/07/2023.

Anon. Avanafil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/07/2023.

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