var-DEN-a-fil

Therapeutic Classification:erectile dysfunction agents

Pharmacologic Classification: phosphodiesterase type 5 inhibitors

• Erectile dysfunction (ED).

• Increases cyclic guanosine monophosphate (cGMP) levels by inhibiting phosphodiesterase type 5, an enzyme responsible for the breakdown of cGMP. cGMP produces smooth muscle relaxation of the corpus cavernosum, which in turn promotes increased blood flow and subsequent erection.

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

Absorption: 15% absorbed following oral administration; absorption is rapid.

Distribution: Extensive tissue distribution; penetrates semen.

Protein Binding: 95%.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP3A4 isoenzyme and to a lesser extent by the CYP2C isoenzyme. M1 metabolite has anti-erectile dysfunction activity. Parent drug and metabolites are mostly excreted in feces. 2–6% renally eliminated.

Half-life: 4–6 hr.

Contraindicated in:

• Hypersensitivity
• Concurrent use of nitrates or riociguat
• Unstable angina, recent history of stroke, life-threatening arrhythmias, HF or MI within 6 mo
• End-stage renal disease requiring dialysis
• Known hereditary degenerative retinal disorders
• Moderate hepatic impairment (orally disintegrating tablets only)
• Severe hepatic impairment
• Congenital or acquired QT prolongation or concurrent use of Class IA or III antiarrhythmics.

Use Cautiously in:

• Other serious underlying cardiovascular disease or left ventricular outflow obstruction
• Penile deformity
• Underlying conditions predisposing to priapism, including sickle cell anemia, multiple myeloma, or leukemia
• Bleeding disorders or active peptic ulcer diseases
• 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)
• Geri: Older adults may have ↑ levels; ↓ dose required.

Derm: flushing.

EENT: HEARING LOSS, rhinitis, sinusitis, VISION LOSS.

GI: dyspepsia, nausea.

GU: priapism.

Neuro: headache, amnesia, dizziness.
Misc: flu syndrome.

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.
• Concurrent use of Class IA antiarrhythmics (such as quinidine or procainamide) or Class III antiarrhythmics (such as amiodarone or sotalol) ↑ risk of serious arrhythmias and should be avoided.
• Concurrent use of alpha-adrenergic blockers may cause serious hypotension; lowest doses of each should be used initially.
• Strong CYP3A4 inhibitors, including atazanavir, clarithromycin, cobicistat, itraconazole, ketoconazole, and ritonavir, may ↑ levels and the risk of toxicity; concurrent use of moderate CYP3A4 inhibitors, including erythromycin, may also ↑ levels and the risk of toxicity; avoid concurrent use with Staxyn; dose of Levitra must be ↓.
• ↑risk of hypotension with alpha-adrenergic blockers and acute ingestion of alcohol; patients should be on stable dose of alpha blockers before starting vardenafil (should start therapy with tablets [orally disintegrating tablets should not be used]).

Tablets

• PO (Adults): 10 mg taken 1 hr prior to sexual activity (range 5–20 mg; not to exceed one dose/24 hr); Concurrent use of cobicistat or ritonavir: single dose should not exceed 2.5 mg in any 72-hr period; Concurrent use of atazanavir, clarithromycin, ketoconazole 400 mg daily, or itraconazole 400 mg daily: single dose should not exceed 2.5 mg/24 hr; Concurrent use of ketoconazole 200 mg daily, itraconazole 200 mg daily, or erythromycin: single dose should not exceed 5 mg/24 hr; Concurrent use of stable alpha-blocker therapy (not on potent CYP3A4 inhibitor): 5 mg initial dose; titrate as tolerated; Concurrent use of stable alpha-blocker and potent CYP3A4 inhibitor therapy: 2.5 mg initial dose; titrate as tolerated.
• PO (Geriatric Patients 65 yr): 5 mg initial dose; titrate as tolerated.

Orally Disintegrating Tablets

• PO (Adults): 10 mg taken 1 hr prior to sexual activity (not to exceed one dose/24 hr).

(Generic available)

• Tablets: 2.5 mg; 5 mg; 10 mg; 20 mg;
• Orally disintegrating tablets (peppermint flavor): 10 mg;

• Assess for the presence of ED before administration. Vardenafil has no effect in the absence of sexual stimulation.

• Tablets and orally disintegrating tablets are not interchangeable.
• PO: Tablets are usually administered 1 hr before sexual activity. May be administered 30 min to 4 hr before sexual activity.
  • Administer orally disintegrating tablets 1 hr before sexual activity. These tablets should be left in the package until use. Remove from the blister pouch. Do not push tablet through the blister; peel open the blister pack with dry hands and place tablet on tongue. Tablet will dissolve rapidly and be swallowed with saliva. No liquid is needed to take the orally disintegrating tablet.
  • May be administered without regard to food.

• Instruct patient to take vardenafil approximately 30 min–1 hr before sexual activity and not more than once per day. Inform patient that sexual stimulation is required for an erection to occur after taking vardenafil.
• Advise patient that vardenafil is not indicated for use in women.
• Caution patient not to take vardenafil concurrently with alpha adrenergic blockers (unless on a stable dose) or nitrates. If chest pain occurs after taking vardenafil, instruct patient to seek immediate medical attention.
• Instruct patient to notify health care professional promptly if erection lasts longer than 4 hr or if sudden or decreased vision loss in one or both eyes, or loss or decrease in hearing, ringing in the ears, or dizziness occurs.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Inform patient that vardenafil 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.

Levitra, Staxyn