avanafil


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avanafil

Stendra

Pharmacologic class: Phosphodiesterase type 5 (PDE5) inhibitor

Therapeutic class: Erectile dysfunction agent

Pregnancy risk category C

Action

Enhances the effect of nitric oxide by inhibiting PDE5, which is responsible for degradation of cyclic guanosine monophosphate in the corpus cavernosum. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has no effect in the absence of sexual stimulation.

Availability

Tablets: 50 mg, 100 mg, 200 mg

Indications and dosages

Erectile dysfunction

Adults: Initially, 100 mg P.O. approximately 30 minutes before sexual activity on an as-needed basis. May increase dosage to 200 mg or decrease to 50 mg based on efficacy or tolerability; use the lowest dosage that provides benefit. Not to exceed one dose daily.

Dosage adjustment

• Concurrent use of moderate CYP3A4 inhibitors
• Concurrent use of alpha blockers

Contraindications

• Hypersensitivity to drug or its components
• Concurrent use of any form of organic nitrates

Precautions

Use cautiously in:
• severe hepatic or renal impairment (avoid use)
• mild to moderate hepatic or renal impairment
• patients in whom sexual activity is inadvisable due to CV status (particularly those with left ventricular outflow obstruction, such as aortic stenosis or idiopathic hypertrophic subaortic stenosis, and those with severely impaired autonomic blood pressure control)
• patients who have suffered MI, stroke, life-threatening arrhythmia, or coronary revascularization within the last 6 months; patients with resting hypotension (blood pressure less than 90/50 mm Hg) or hypertension (blood pressure greater than 170/100 mm Hg); patients with unstable angina, angina with sexual intercourse, or New York Heart Association Class 2 or greater congestive heart failure; patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa (use not recommended)
• patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease); patients who have conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia); patients with bleeding disorders or active peptic ulceration
• concurrent use of strong CYP3A4 inhibitors, CYP 450 inducers, or other PDE5 inhibitors, or erectile dysfunction therapies (use not recommended)
• concurrent use of moderate CYP3A4 inhibitors
• concurrent use of CYP3A4 inducers (not recommended)
• concurrent use of alpha blockers or other antihypertensives or substantial amounts of alcohol
• elderly patients
• women (not indicated)
• children younger than age 18 (safety and efficacy not established).

Administration

Don't give concurrently with nitrates. In a patient who has taken this drug, where nitrate administration is deemed medically necessary in a life-threatening situation, allow at least 12 hours to elapse after the last dose of avanafil before considering nitrate administration. In such circumstances, administer nitrates under close medical supervision with appropriate hemodynamic monitoring.

Adverse reactions

CNS: headache, dizziness

CV: hypertension, ECG abnormality

EENT: sudden decrease or loss of hearing, tinnitus, nasal congestion, nasopharyngitis, sinusitis, sinus congestion

GI: dyspepsia, nausea, constipation, diarrhea

GU: priapism

Musculoskeletal: back pain, arthralgia

Respiratory: upper respiratory tract infection, bronchitis

Skin: flushing, rash, pruritus

Other: influenza, hypersensitivity

Interactions

Drug-drug.Alpha blockers (such as alfuzosin, tamsulosin), antihypertensives, nitrates (such as isosorbide, nitroglycerin): increased risk of hypotension

Amlodipine: increased avanafil Cmax and area under the curve (AUC)

CYP2C8 substrates (rosiglitazone): increased rosiglitazone AUC and decreased rosiglitazone Cmax

Desipramine, omeprazole: increased AUC and Cmax of these drugs

Moderate CYP3A4 inhibitors (such as amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil), strong CYP3A4 inhibitors (such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, ritonavir, saquinavir, telithromycin): increased avanafil plasma concentration

Drug-food. Grapefruit juice: potentially increased avanafil exposure

High-fat diet: reduced drug absorption, decreased peak level

Drug-behaviors.Alcohol use (substantial amounts): increased risk of hypotension

Patient monitoring

• Monitor CV status carefully.
• Monitor patient's hearing.

Patient teaching

• Tell patient to take tablets with or without food but not to take with grapefruit juice.
• Tell patient that high-fat diet may interfere with drug efficacy.
• Advise patient to take drug 30 minutes before sexual activity.
• Tell patient not to exceed prescribed dosage or take more than one dose daily.

Instruct patient to stop sexual activity and contact prescriber immediately if chest pain, dizziness, or nausea occurs.

Teach patient to recognize and immediately report serious cardiac and vision problems, and sudden decrease in or loss of hearing.

Caution patient never to take drug with nitrates, because of risk of significant hypotension.
• Advise patient to avoid or limit alcohol use, because substantial use may cause increase in heart rate, decrease in standing blood pressure, dizziness, and headache.
• Inform patient that this drug can cause serious interactions with many common drugs. Instruct him to tell all prescribers he's taking avanafil.
• Instruct patient not to take other erectile dysfunction drugs while taking this drug.
• Instruct patient to report priapism (persistent, painful erection) or erections lasting more than 4 hours.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs, foods, and behaviors mentioned above.

avanafil

(av-an-a-fil) ,

Stendra

(trade name)

Classification

Therapeutic: erectile dysfunction agents
Pharmacologic: phosphodiesterase type 5 inhibitors
Pregnancy Category: C

Indications

Treatment of erectile dysfunction.

Action

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.

Therapeutic effects

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

Pharmacokinetics

Absorption: Rapidly absorbed following oral administration.
Distribution: Minimal amounts enter semen.
Protein Binding: 99%.
Metabolism and 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.

Time/action profile (effect on BP)

ROUTEONSETPEAKDURATION
POwithin 1 hr1–2 hrunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Concurrent organic nitrate therapy (nitroglycerin, isosorbide mononitrate, isosorbide dinitrate);Severe renal or hepatic impairment;Concurrent strong inhibitors of the CYP3A4 enzyme system;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
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;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 moderate inhibitors of the CYP3A4 enzyme system (initiate with 50 mg dose);History of hearing loss;Bleeding disorders or peptic ulceration; Geriatric: Elderly may be more sensitive to drug effects;Not intended for use in women; Pediatric: Safe use in children <18 yr not established.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)
  • dizziness

Ear, Eye, Nose, Throat

  • nasal congestion
  • nasopharyngitis
  • sudden hearing/vision loss

Genitourinary

  • priapism

Dermatologic

  • flushing (most frequent)

Musculoskeletal

  • back pain

Interactions

Drug-Drug interaction

Blood levels and effects may be ↑ by CYP3A4 inhibitors, concurrent use of strong CYP3A4 inhibitors including atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, saquinavir, and telithromycin is contraindicated.A similar but lesser effect is expected with moderate CYP3A4 inhibitors including erythromycin, aprepitant, diltiaziem. fluconazole, fosamprenavir, ritonavir and verapamil ; initial dose should not exceed 50 mg/24 hr.↑ risk of hypotension with nitrates, alpha-adrenergic blockers, antihypertensives and alcohol (more than 3 units); concurrent use with nitrates is contraindicated, dosage adjustments may be necessary with others.If nitrates are medically necessary, at 12 hr should pass following avanafil adminitration.

Route/Dosage

Oral (Adults) 100 mg 30 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.

Availability

Tablets: 50 mg, 100 mg, 200 mg

Nursing implications

Nursing assessment

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

Potential Nursing Diagnoses

Sexual dysfunction (Indications)
Ineffective tissue perfusion (Adverse Reactions)

Implementation

  • Oral: Administer dose as needed for ED at least 30 min prior to sexual activity
    • May be administered without regard to food.

Patient/Family Teaching

  • Instruct patient to take avanafil as needed for ED at least 30 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.

Evaluation/Desired Outcomes

  • Male erection sufficient to allow intercourse.
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References in periodicals archive ?
It does not appear that the vasodilator avanafil (Stendra; impotence agent) will be used in pregnancy.
has entered into a Commercial Supply Agreement with Sanofi Chimie ("Sanofi"), a wholly owned subsidiary of Sanofi, to manufacture and supply the active pharmaceutical ingredient (API) for avanafil on an exclusive basis in the United States and other territories and on a semi-exclusive basis in the European Union and Latin America.
The new drug Stendra, the brand name for avanafil, is the first new erectile dysfunction drug in a decade for this class of drugs called phosphodiesterase type 5 (PDE5) inhibitors.
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The growth in the market between 2005 and 2010 was attributed to the increasing elderly population and the expected launch of avanafil in 2013 in the US.
TM)], the trade name for avanafil in the European Union (EU), is approved by the European Medicines Agency (EMA) for the treatment of ED in the EU.
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One of the promising molecules is Avanafil, which is unlikely to have much impact as the market has high competition among similar products and will experience generic erosion after 2012 due to patent expiry of Viagra.
The Efficacy of Avanafil in Subjects with Intercourse Attempts Within 15 Minutes After Dosing : Moderated Posters 5: ED Diagnosis & Medical Treatment, Saturday, November 22, 11:10 a.
The manufacturers claim that avanafil works faster than drugs like Levitra currently on the market.
Nasdaq:VVUS) we discuss their Avanafil as well as their upcoming FDA Advisory panel on Qnexa.