Avanafil

Pronunciation: a-VAN-a-fil
Class: Phosphodiesterase type 5 inhibitor

Trade Names

Stendra
- Tablets, oral 50 mg
- Tablets, oral 100 mg
- Tablets, oral 200 mg

Pharmacology

Enhances the effect of nitric oxide by inhibiting phosphodiesterase 5 (PDE5) in the corpus cavernosum.

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Pharmacokinetics

Absorption

Rapidly absorbed with a median T max of 30 to 45 min.

Distribution

About 99% bound to plasma proteins.

Metabolism

Extensively metabolized by CYP3A4 enzyme and to a minor extent by CYP2C isoform. Major circulating metabolites are M4 and M16 and are about 23% and 29% that of the parent compound, respectively.

Elimination

The terminal elimination half-life is about 5 h. Avanafil is excreted as metabolites, mainly in the feces (approximately 62%) and to a lesser extent in the urine (approximately 21%).

Special Populations

Renal Function Impairment

In mild renal impairment, AUC 0-inf decreased by 2.9% and C max increased by 2.8%; in moderate renal impairment, AUC 0-inf increased by 9.1% and C max decreased by 2.8%.

Hepatic Function Impairment

In mild hepatic impairment, AUC 0-inf increased by 3.8% and C max decreased by 2.7%; in moderate hepatic impairment, AUC 0-inf increased by 11.2% and C max decreased by 51%.

Elderly

AUC 0-inf increased by 6.8% and C max decreased by 2.1%.

Indications and Usage

For the treatment of erectile dysfunction.

Contraindications

Coadministration with any form of organic nitrates, either regularly and/or intermittently; known hypersensitivity to any component of the tablet.

Dosage and Administration

Adults

PO Initially, 100 mg as needed approximately 30 min before sexual activity. The dose may be increased to a max dose of 200 mg or decreased to 50 mg.

Concomitant therapy
Adults Alpha-blockers

PO Patients should be stable on alpha-blocker therapy prior to starting avanafil. Avanafil should be initiated at the 50 mg dose.

Moderate CYP3A4 inhibitors (eg, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil)

PO Max dosage of avanafil is 50 mg once every 24 h.

Nitrates

PO Concomitant use with nitrates in any form is contraindicated.

Strong CYP3A4 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)

PO Avoid use.

General Advice

  • May be taken without regard to food.
  • Maximum dosing frequency is once per day.
  • The lowest dose that provides benefit should be used.
  • Sexual stimulation is required for a response to treatment.

Storage/Stability

Store between 68° and 86°F. Protect from light.

Drug Interactions

Alcohol

The BP-lowering effects of both alcohol and avanafil may be increased. Drinking more than 3 units of alcohol (eg, 3 glasses of wine) with avanafil may increase the risk of orthostatic signs and symptoms, including increased heart rate, decreased standing BP, dizziness, and headache.

Alpha-blockers (eg, doxazosin, terazosin)

Concomitant use may lower BP, which may lead to symptomatic hypotension (eg, fainting). Use with caution; initiate avanafil only in patients who are stable on alpha-blocker therapy. Initiate avanafil therapy at the 50 mg dose. In patients already receiving an optimized dose of avanafil, alpha-blocker therapy should be started at the lowest dose.

Antihypertensive agents (eg, amlodipine, enalapril)

Coadministration may increase the risk of hypotension. Use with caution. Closely monitor BP. In addition, amlodipine may increase avanafil AUC and C max and prolong the half-life while the AUC and C max of amlodipine may be decreased slightly.

CYP inducers

The effects on avanafil pharmacokinetics have not been evaluated. Coadministration is not recommended.

CYP3A4 moderate inhibitors (eg, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil)

Avanafil plasma concentrations may be increased and the half-life prolonged. For patients taking moderate CYP3A4 inhibitors, the maximum recommended starting dose of avanafil is 50 mg, not to be exceeded once every 24 h.

CYP3A4 strong inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)

Avanafil plasma concentrations may be increased and the half-life prolonged. Avoid coadministration.

Grapefruit juice

Although specific interactions have not been studied, grapefruit juice, a CYP3A4 inhibitor, would likely increase avanafil exposure. Clinical monitoring for signs of avanafil toxicity is warranted.

Nitrates (eg, isosorbide, nitroglycerin)

The hypotensive effects of nitrates may be potentiated. Coadministration is contraindicated. If concurrent use is deemed medically necessary in a life-threatening situation, ensure that at least 12 h elapse after the last dose of avanafil before nitrate administration is considered.

Other erectile dysfunction therapies (eg, sildenafil)

The safety and efficacy of concurrent therapy have not been studied. Coadministration is not recommended.

Sodium nitroprusside

In vitro studies with human platelets indicated that avanafil potentiates the antiaggregatory effect of sodium nitroprusside.

Adverse Reactions

Cardiovascular

Flushing (10%); abnormal ECG (3%); hypertension (1% to less than 2%).

CNS

Headache (12%); dizziness (2%).

EENT

Nasopharyngitis (5%); nasal congestion (3%); sinusitis, sinus congestion (1% to less than 2%).

GI

Constipation, diarrhea, dyspepsia, nausea (1% to less than 2%).

Musculoskeletal

Back pain (3%); arthralgia (1% to less than 2%).

Respiratory

Upper respiratory tract infection (3%); bronchitis (1% to less than 2%).

Miscellaneous

Influenza, rash (1% to less than 2%).

Precautions

Monitor

Monitor patients for response to therapy, any changes in BP or heart rate, and hearing or vision loss.


Pregnancy

Category C . Avanafil is not indicated for use in women.

Lactation

Undetermined. Avanafil is not indicated for use in women.

Children

Not indicated for use in pediatric patients. Safety and efficacy not established.

Elderly

A greater sensitivity to medications in some older individuals should be considered.

Hypersensitivity

Has been reported, including pruritus and eyelid swelling.

Renal Function

Do not use in patients with severe renal disease or on renal dialysis.

Hepatic Function

Do not use in patients with severe hepatic disease.

CV effects

Patients with left ventricular outflow obstruction (eg, aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of BP can be particularly sensitive to the action of vasodilators, including avanafil. Use is not recommended in patients with unstable angina or angina occurring during sexual intercourse; New York Heart Association class II or higher CHF; MI, stroke, life-threatening arrhythmia, or coronary revascularization within the last 6 mo; hypotension (less than 90/50 mm Hg) or hypertension (more than 170/100 mm Hg).

Hematologic effects

Safety of avanafil is unknown in patients with bleeding disorders or active peptic ulceration.

Ophthalmic effects

Sudden loss of vision in one or both eyes has been reported rarely and may be a sign of nonarteritic anterior optic neuropathy. Use is not recommended in patients with degenerative retinal disorders, including retinitis pigmentosa.

Otic effects

Sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, has been reported.

Priapism

Prolonged erections exceeding 4 h and painful erections greater than 6 h in duration may occur and require immediate medical attention. Use with caution in patients with conditions that may predispose them to priapism (eg, sickle cell anemia, multiple myeloma, leukemia) and in patients with anatomical deformation of the penis (eg, angulation, cavernosal fibrosis, Peyronie disease).

Overdosage

Symptoms

Single doses of up to 800 mg have been given to healthy subjects, and multiple doses of up to 300 mg have been given to patients.

Patient Information

  • Discuss with patients the contraindication of avanafil with regular and/or intermittent use of organic nitrates.
  • Discuss with patients the potential cardiac risk of sexual activity in patients with preexisting CV risk factors.
  • Discuss with patients the potential for avanafil to augment the BP-lowering effect of alpha-blockers and other antihypertensive medications.
  • Advise patient to contact their health care provider if new medications that may interact with avanafil are prescribed by another health care provider.
  • Advise patients that there have been rare reports of prolonged erections longer than 4 h in duration and priapism (painful erections longer than 6 h in duration) for this class of compounds. Advise patients who have an erection lasting longer than 4 h, whether painful or not, to seek emergency medical attention.
  • Advise patients to stop use of all PDE5 inhibitors, including avanafil, and seek medical attention in the event of a sudden loss of vision in one or both eyes or a sudden decrease or loss of hearing.
  • Inform patients that substantial consumption of alcohol (eg, greater than 3 units) in combination with avanafil can increase the potential for orthostatic signs and symptoms.
  • Caution patients that medication does not provide protection against STDs, and to use protective measures as indicated.
  • Advise patients to take prescribed dose at least 30 min before anticipated sexual activity. Advise patients that sexual stimulation will be required for medication to work and an erection to occur.

Copyright © 2009 Wolters Kluwer Health.

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