av-AN-a-fil

Therapeutic Classification:erectile dysfunction agents

Pharmacologic Classification: phosphodiesterase type 5 inhibitors

• Treatment of erectile dysfunction.

• Enhances effects of nitric oxide released during sexual stimulation. Nitric oxide activates guanylate cyclase, which produces ↑ levels of cyclic guanosine monophosphate (cGMP). cGMP produces smooth muscle relaxation of the corpus cavernosum, which promotes ↑ blood flow and subsequent erection. Inhibits the enzyme phosphodiesterase type 5 (PDE5), PDE5 inactivates cGMP.

• Enhanced blood flow to the corpus cavernosum and erection sufficient to allow sexual intercourse. Requires sexual stimulation.

Absorption: Rapidly absorbed following oral administration.

Distribution: Minimal amounts enter semen.

Protein Binding: 99%.

Metabolism/Excretion: Mostly metabolized by the liver (primarily by the CYP3A4 enzyme system), metabolites excreted in feces (62%) and urine (21%). One metabolite had inhibitory activity on PDE5.

Half-life: 5 hr.

(effect on BP)

Contraindicated in:

• Hypersensitivity
• Concurrent use of nitrates, riociguat, or vericiguat
• Severe renal or hepatic impairment
• Concurrent use of strong CYP3A4 inhibitors
• Serious underlying cardiovascular disease (including history of MI, stroke, or serious arrhythmia within 6 mo), cardiac failure, or coronary artery disease with unstable angina, angina with sexual intercourse
• History of HF, coronary artery disease, uncontrolled hypertension (BP >170/110 mm Hg) or hypotension (BP <90/50 mm Hg), dehydration, autonomic dysfunction, or severe left ventricular outflow obstruction
• Hereditary degenerative retinal disorders
• Women.

Use Cautiously in:

• Serious underlying cardiovascular disease or conditions in which sexual activity is not advised
• History of sudden severe vision loss or non-arteritic ischemic optic neuropathy (NAION); may ↑ risk of recurrence
• Low cup to disk ratio, age >50 yr, diabetes, hypertension, coronary artery disease, hyperlipidemia, or smoking (↑ risk of NAION)
• Alpha adrenergic blockers (patients should be on stable dose of alpha blockers before treatment, initiate with 50 mg dose)
• Anatomic penile deformity (angulation, cavernosal fibrosis, Peyronie disease)
• Conditions associated with priapism (sickle cell anemia, multiple myeloma, leukemia)
• Concurrent use of moderate CYP3A4 inhibitors (initiate with 50 mg dose)
• History of hearing loss
• Bleeding disorders or peptic ulceration
• Pedi: Safety not established in children
• Geri: older adults may be more sensitive to drug effects.

Derm: flushing.

EENT: nasal congestion, nasopharyngitis, sudden hearing/vision loss.

GU: priapism.

MS: back pain.

Neuro: headache, dizziness.

Drug-Drug:

• Concurrent use of nitrates may cause serious, life-threatening hypotension and is contraindicated.
• Concurrent use of riociguat or vericiguat may result in severe hypotension; concurrent use contraindicated.
• Blood levels and effects may be ↑ by CYP3A4 inhibitors, concurrent use of strong CYP3A4 inhibitors including atazanavir, clarithromycin, itraconazole, ketoconazole, nefazodone, and nelfinavir is contraindicated.
• A similar but lesser effect is expected with moderate CYP3A4 inhibitors including erythromycin, aprepitant, diltiazem, fluconazole, fosamprenavir, ritonavir, and verapamil; initial dose should not exceed 50 mg/24 hr.
• ↑risk of hypotension with alpha-adrenergic blockers, antihypertensives, and alcohol (more than 3 units); dosage adjustments may be necessary.

• PO (Adults): 100 mg 15 min prior to sexual activity, not to exceed once daily (range 50–200 mg, use lowest effective dose); Concurrent alpha-blockers or moderate CYP3A4 inhibitors: 50 mg, not to exceed once daily.

• Tablets: 50 mg; 100 mg; 200 mg;

• Determine erectile dysfunction before administration. Avanafil has no effect in the absence of sexual stimulation.

• PO: Administer dose as needed for erectile dysfunction at least 15 min prior to sexual activity.
  • May be administered without regard to food.

• Instruct patient to take avanafil as needed for ED at least 15 min before sexual activity and not more than once per day. Inform patient that sexual stimulation is required for an erection to occur after taking avanafil.
• Advise patient that avanafil is not indicated for use in women.
• Caution patient not to take avanafil concurrently with alpha adrenergic blockers (unless on a stable dose) or nitrates. If chest pain occurs after taking avanafil, instruct patient to seek immediate medical attention.
• Advise patient to avoid excess alcohol intake (3 units) in combination with avanafil; may increase risk of orthostatic hypotension, increased heart rate, decreased standing BP, dizziness, headache.
• Instruct patient to notify health care professional promptly if erection lasts longer than 4 hr, if they are not satisfied with their sexual performance, develop unwanted side effects or if they experience sudden or decreased vision loss in one or both eyes or loss or decrease in hearing, ringing in the ears, or dizziness.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications that may interact with avanafil.
• Inform patient that avanafil offers no protection against sexually transmitted diseases. Counsel patient that protection against sexually transmitted diseases and HIV infection should be considered.

• Male erection sufficient to allow intercourse.

Stendra