avanafil, Stendra

 Indications

Treatment of erectile dysfunction.

Action

Enhances effects of nitric oxide released during sexual

stimulation. Nitric oxide activates guanylate cyclase,

which producesqlevels of cyclic guanosine monophosphate

(cGMP). cGMP produces smooth muscle relaxation

of the corpus cavernosum, which promotesq

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)

ROUTE ONSET PEAK DURATION

PO within 1 hr 1–2 hr unknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent

use of nitrates or riociguat; 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); mayqrisk

of recurrence; Low cup to disk ratio, age 50 yr, diabetes,

hypertension, coronary artery disease, hyperlipidemia,

or smoking (qrisk 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; Geri: Elderly

may be more sensitive to drug effects; Pedi: Safety not

established.

Adverse Reactions/Side Effects

CNS: headache, dizziness. EENT: nasal congestion,

nasopharyngitis, sudden hearing/vision loss. GU: priapism.

Derm: flushing. MS: back pain.

Interactions

Drug-Drug: Concurrent use of nitrates may cause

serious, life-threatening hypotension and is contraindicated.

Concurrent use of riociguat may result in severe

hypotension; concurrent use contraindicated. Blood

levels and effects may beqby CYP3A4 inhibitors,

concurrent use of strong CYP3A4 inhibitors including

atazanavir, clarithromycin, indinavir, itraconazole,

ketoconazole, nefazodone, nelfinavir, and

saquinavir 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.qrisk

of hypotension with alpha-adrenergic blockers,

antihypertensives, and alcohol (more than 3 units);

dosage adjustments may be necessary.

Route/Dosage

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.

Availability

Tablets: 50 mg, 100 mg, 200 mg.