Pronunciation: var-DEN-a-fil HYE-droe-KLOR-ide
Class: Phosphodiesterase type 5 inhibitor

Trade Names

Levitra
- Tablets, oral 2.5 mg
- Tablets, oral 5 mg
- Tablets, oral 10 mg
- Tablets, oral 20 mg

Staxyn
- Tablets, orally disintegrating 10 mg

Pharmacology

Enhances the effect of nitric oxide at the nerve ending and endothelial cells in the corpus cavernosum by inhibiting phosphodiesterase type 5 (PDE5) in the corpus cavernosum of the penis. This results in vasodilation, increased inflow of blood into the corpora cavernosa, and penile erection upon sexual stimulation.

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Pharmacokinetics

Absorption

Rapidly absorbed with bioavailability of approximately 15% ( Levitra ). C _max reached between 30 min and 2 h after an oral dose of Levitra and between 45 min and 2.5 h for Staxyn . High-fat meals reduced C _max by 18% to 50% ( Levitra ) and 35% ( Staxyn ).

Distribution

Vd _ss is 208 L. Protein binding is approximately 95%.

Metabolism

Metabolized predominately by CYP3A4 and to a lesser degree by CYP3A5 and CYP2C isoforms. The major metabolite (M1) accounts for 7% of the total activity.

Elimination

Excretion as metabolites (91% to 95% in feces, 2% to 6% in urine). Total body Cl is 56 L/h. Half-life and M1 is approximately 4 to 5 h for Levitra and approximately 4 to 6 h (3 to 5 h for M1) for Staxyn .

Special Populations

Renal Function Impairment

The AUC was 20% to 30% higher in moderate (CrCl 30 to 50 mL/min) and severe (CrCl less than 30 mL/min) renal impairment. Vardenafil pharmacokinetics have not been evaluated in patients requiring renal dialysis.

Hepatic Function Impairment

In patients with mild hepatic impairment (Child-Pugh class A), C _max and AUC increased by 22% and 17%, respectively. In patients with moderate hepatic impairment (Child-Pugh class B), C _max and AUC increased by 130% and 160%, respectively. Levitra has not been evaluated in patients with severe (Child-Pugh class C) hepatic impairment. Do not use Staxyn in patients with moderate or severe hepatic impairment.

Elderly

In men 65 y and older, the C _max and AUC are increased 34% and 52%, respectively, for Levitra and by 21% and 39%, respectively, for Staxyn compared with men younger than 45 y. Consider a lower starting dose of Levitra 5 mg in patients 65 y and older.

Children

Vardenafil is not indicated for use in children.

Indications and Usage

Treatment of erectile dysfunction.

Unlabeled Uses

Raynaud phenomenon ( Levitra only).

Contraindications

Administration with nitrates and nitric oxide donors; hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO 10 mg approximately 60 min prior to sexual activity. Depending on efficacy and adverse reactions, Levitra may be decreased to 5 mg or increased to 20 mg. Max dosage is 20 mg once daily ( Levitra ) or 10 mg/day ( Staxyn ).

Elderly (65 y and older)

PO A 5 mg starting dose is recommended.

Hepatic Function Impairment
Adults

PO A 5 mg ( Levitra ) starting dose is recommended in patients with moderate hepatic impairment (max, 10 mg). Do not use Staxyn in patients with moderate or severe hepatic impairment.

Concomitant Therapy
Adults Alpha-blockers

PO In those patients who are stable on alpha-blocker therapy, Levitra should be initiated at a dose of 5 mg (2.5 mg when used concomitantly with certain CYP3A4 inhibitors). Do not initiate Staxyn in patients taking alpha-blockers; use Levitra as initial therapy in these patients.

CYP3A4 inhibitors

PO For ritonavir, a single dose of Levitra 2.5 mg should not be exceeded in a 72-h period. For indinavir, saquinavir, atazanavir, clarithromycin, ketoconazole 400 mg daily, and itraconazole 400 mg daily, a single dose of Levitra 2.5 mg should not be exceeded in a 24-h period. For ketoconazole 200 mg daily, itraconazole 200 mg daily, and erythromycin, a single dose of Levitra 5 mg should not be exceeded in a 24-h period. Do not use Staxyn with potent or moderate CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, atazanavir, clarithromycin, erythromycin).

Nitrates

PO Concomitant use with nitrates in any form is contraindicated.

General Advice

• May be taken with or without food.
• Administer orally, as needed, approximately 60 min before sexual activity.
• Staxyn should be placed on the tongue, where it will disintegrate. It should be taken without liquid immediately upon removal from the blister.
• Staxyn is not interchangeable with Levitra .

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Alpha-blockers (eg, terazosin)

Risk of hypotension is increased. Use with caution. Concomitant treatment with vardenafil and alpha-blockers should be initiated only if the patient is stable on alpha-blocker therapy. Initiate vardenafil therapy at the lowest recommended dose.

Antihypertensive agents (eg, nifedipine)

Vardenafil may add to the BP-lowering effects of antihypertensive agents. Dosage adjustments may be needed.

Class IA (eg, quinidine, procainamide) and class III (eg, amiodarone, sotalol) antiarrhythmic agents

Patients with congenital QT prolongation and those receiving these agents should avoid use of vardenafil.

CYP-450 3A4/5 and CYP2C9 (eg, ciprofloxacin, clarithromycin, erythromycin, itraconazole, ketoconazole, protease inhibitors [eg, atazanavir, indinavir, ritonavir, saquinavir]) inhibitors

Plasma levels of vardenafil may be elevated, increasing the risk of adverse reactions and necessitating dosage adjustment. Protease inhibitor plasma concentrations may also be decreased. Dosage adjustment may be needed.

Nitrates

Coadministration with vardenafil is contraindicated. Risk of hypotension is increased.

Adverse Reactions

Cardiovascular

Angina pectoris, chest pain, hypertension, hypotension, MI, myocardial ischemia, palpitation, postural hypotension, syncope, tachycardia, ventricular tachyarrhythmias (less than 2%).

CNS

Headache (15%); dizziness (2%); amnesia, asthenia, dysesthesia, hypertonia, hypesthesia, insomnia, paresthesia, seizure, sleep disorder, somnolence, vertigo (less than 2%); seizure recurrence (postmarketing).

Dermatologic

Erythema, photosensitivity reaction, pruritus, rash, sweating (less than 2%).

EENT

Rhinitis (9%); nasal congestion, sinusitis (3%); abnormal vision, blurred vision, chromatopsia, color vision changes, conjunctivitis, dim vision, eye discomfort, eye pain, glaucoma, increased IOP, increased redness of the eye, ocular hyperemia, pharyngitis, photophobia, sinus congestion, sudden decrease or loss of hearing, tinnitus, vision color distortions, visual disturbance, watery eyes (less than 2%); reduced visual acuity, retinal vein occlusion, vision loss (temporary or permanent), visual field defect (postmarketing).

GI

Dyspepsia (4%); nausea (2%); abdominal pain, diarrhea, dry mouth, dysphagia, esophagitis, gastritis, gastroesophageal reflux, GI pain, nausea, vomiting (less than 2%).

Genitourinary

Abnormal ejaculation, increase in erections, priapism (less than 2%).

Hepatic

Abnormal LFTs, gamma-glutamyl-transpeptidase increase, increases in transaminases (less than 2%).

Hypersensitivity

Allergic edema, allergic reactions, anaphylactic reactions (including laryngeal edema), angioedema (less than 2%).

Lab Tests

Increased creatine kinase (2%).

Musculoskeletal

Back pain (2%); arthralgia, increased CPK, increased muscle tone and cramping, myalgia, neck pain (less than 2%).

Respiratory

Dyspnea, epistaxis (less than 2%).

Miscellaneous

Flushing (11%); accidental injury, flu syndrome (3%); face edema, feeling unwell, pain (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 B .

Lactation

Undetermined.

Children

Not indicated for use in children.

Elderly

Because men 65 y and older may have higher plasma levels, a lower starting dose is recommended.

Renal Function

Do not use in patients on renal dialysis.

Hepatic Function

Reduce starting dose in patients with moderate hepatic impairment. Do not use Levitra in patients with severe hepatic impairment. Do not use Staxyn in patients with moderate or severe hepatic impairment.

Anatomical deformation of the penis

Use with caution in patients with anatomical deformation of the penis (eg, angulation, cavernosal fibrosis, Peyronie disease) or patients prone to priapism (eg, leukemia, multiple myeloma, sickle cell anemia).

Bleeding disorders

Administer with caution to patients with bleeding disorders or significant active peptic ulceration.

Cardiac risk

Evaluate CV status, history of QT prolongation, left ventricular outflow obstruction (eg, aortic stenosis, idiopathic hypertrophic subaortic stenosis), and BP before treatment.

Fructose intolerance

Staxyn tablets contain sorbitol; do not use in patients with a rare hereditary problem of fructose intolerance.

Hearing loss

Sudden decrease in hearing or hearing loss may occur and may be accompanied by tinnitus and dizziness.

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.

Phenylketonurics

Staxyn tablets contain aspartame, a source of phenylalanine, which may be harmful for people with phenylketonuria.

Priapism

Prolonged erections (exceeding 4 h) and priapism (painful erections longer than 6 h) may occur and require immediate medical assistance.

Special populations

Because there are no clinical data on safety and efficacy, use is not recommended in patients with unstable angina, hypotension, uncontrolled hypertension, recent history of stroke, congenital QT prolongation, life-threatening arrhythmia, MI (within the last 6 months), severe cardiac failure, or a known hereditary degenerative retinal disorder, including retinitis pigmentosa.

Overdosage

Symptoms

Abnormal vision, back pain/myalgia.

Patient Information

• Instruct patient to read the patient information leaflet before starting therapy and with each refill.
• Advise patient to take prescribed dose 60 min before anticipated sexual activity and not to take more than 1 dose in a 24-h period.
• Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
• Inform patients that Staxyn tablet should be placed on the tongue, where it will disintegrate, and to take without liquid immediately upon removal from the blister.
• Advise patient that sexual stimulation will be required for medication to work and an erection to occur.
• Instruct patient not to change the dose unless advised by health care provider.
• Advise patient to contact health care provider if they are not satisfied with their sexual performance after taking medication or if bothersome adverse reactions occur.
• Counsel patients that concomitant use of vardenafil with nitrates could cause BP to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke.
• Instruct patient to stop using and contact health care provider immediately if any of the following occur: dizziness, fainting, chest pain, sudden loss or change in vision, sudden decrease in or loss of hearing, erection persisting longer than 4 h, painful erection.
• Inform patients that concomitant use of PDE5 inhibitors, including vardenafil, with alpha-blockers can lower BP significantly, leading to symptomatic hypotension (eg, fainting).
• Advise patients with phenylketonuria that Staxyn tablets contain phenylalanine.
• Caution patient to avoid using “poppers” (eg, amyl nitrate, butyl nitrate) while taking this medication.
• Caution patient that the medication is not a male form of birth control, nor does it provide protection against STDs, and to use protective measures as indicated.

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