avanafil

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

See 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 C_max and area under the curve (AUC)

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

Desipramine, omeprazole: increased AUC and C_max 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.

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

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

See 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.