Vardenafil

Pharmacologic Category

Phosphodiesterase-5 Enzyme Inhibitor

Dosing: Adult

Note: Oral disintegrating tablets should not be used interchangeably with film-coated tablets; patients requiring a dose other than 10 mg should use the film-coated tablets.

Erectile dysfunction: Oral:

Film-coated tablet (Levitra): 10 mg administered ~60 minutes prior to sexual activity; dosing range: 5 to 20 mg; taken as one single dose and not taken more than once daily; maximum 20 mg daily

Oral disintegrating tablet (Staxyn): 10 mg administered ~60 minutes prior to sexual activity; maximum: 10 mg daily

Pulmonary arterial hypertension (off-label use): Oral: 5 mg once daily for 4 weeks, then increase to 5 mg twice daily (Jing 2011).

Raynaud phenomenon (off-label use): Oral: 10 mg twice daily (Caglayan 2006; Caglayan 2012).

Dosing adjustment with concomitant medications:

Alpha-blocker (dose should be stable at time of vardenafil initiation):

Film-coated tablet (Levitra): Initial vardenafil dose: 5 mg taken no more than once daily; if an alpha-blocker is added to vardenafil therapy, it should be initiated at the smallest possible dose and titrated carefully.

Oral disintegrating tablet (Staxyn): Do not use to initiate therapy. Initial therapy should be with film-coated tablets at lower doses. Patients who have previously used film-coated tablets may be switched to oral disintegrating tablets as recommended by healthcare provider. With coadministration, consider a time interval between dosing (eg, 6-hour interval).

CYP3A4 inhibitors:

Film-coated tablet (Levitra): The dosage of vardenafil may require adjustment in patients receiving potent CYP3A4 inhibitors (eg, atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, ritonavir, saquinavir).

For ritonavir, a single dose of vardenafil 2.5 mg should not be exceeded in a 72-hour period.

For indinavir, saquinavir, atazanavir, ketoconazole 400 mg daily, itraconazole 400 mg daily, and clarithromycin, a single dose of vardenafil 2.5 mg should not be exceeded in a 24-hour period.

For ketoconazole 200 mg daily, itraconazole 200 mg daily, and erythromycin, a single dose of vardenafil 5 mg should not be exceeded in a 24-hour period.

Oral disintegrating tablet (Staxyn): Concurrent use not recommended with potent or moderate CYP3A4 inhibitors (atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, ritonavir, saquinavir)

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Erectile dysfunction: Elderly ≥65 years: Film-coated tablet (Levitra): Oral: Consider a starting dose of 5 mg administered ~60 minutes prior to sexual activity; taken as one single dose and not taken more than once daily.

Dosing: Renal Impairment: Adult

Mild, moderate, or severe impairment: No dosage adjustment necessary.

Hemodialysis: Use is not recommended.

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B):

Film-coated tablet (Levitra): Initial: 5 mg administered ~60 minutes prior to sexual activity (maximum dose: 10 mg daily); taken as one single dose and not taken more than once daily

Oral disintegrating tablet (Staxyn): Use is not recommended.

Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).

Use: Labeled Indications

Erectile dysfunction: Treatment of erectile dysfunction (ED)

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Pulmonary arterial hypertensionLevel of Evidence [C]

Data from a small, randomized, double-blinded, placebo-controlled trial suggest that vardenafil may be beneficial for the treatment of pulmonary arterial hypertension (WHO Group I; efficacy established in patients with WHO/NYHA functional class II and III) in adults by improving exercise ability and hemodynamics and delaying clinical worsening Ref.

Raynaud phenomenonLevel of Evidence [B, G]

Data from a meta-analysis and a small, controlled trial support the use of vardenafil for Raynaud phenomenon related to systemic sclerosis, demonstrating a decrease in the frequency and severity of attacks Ref.

Based on the European League Against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis, phosphodiesterase type 5 (PDE5) inhibitors (eg, vardenafil) have been found to reduce the frequency and severity of systemic sclerosis–related Raynaud phenomenon attacks and should be considered in patients with severe symptoms and/or those who do not respond to first-line treatment Ref. Access Full-Off Label Monograph.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Phosphodiesterase Type 5 Inhibitors

Comparative Efficacy

• VARDENAFIL

Clinical Practice Guidelines

Erectile Dysfunction:

AUA, “Erectile Dysfunction,” 2018

“The Princeton III consensus recommendations for the management of erectile dysfunction and cardiovascular disease,” August 2012

Systemic Sclerosis:

EULAR, “Update of EULAR Recommendations for the Treatment of Systemic Sclerosis” August 2017

Administration: Oral

May be administered with or without food, approximately 60 minutes prior to sexual activity.

Oral disintegrating tablet should not be removed from blister pack until administered. Using dry hands, place immediately on tongue. Tablet will dissolve within seconds; do not take with liquid. Do not crush, split, or chew.

Dietary Considerations

Some products may contain phenylalanine. Some products may contain sorbitol; do not use in patients with fructose intolerance.

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Keep oral disintegrating tablets sealed in blisterpack until ready to use.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat erectile dysfunction (ED).

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Flushing

• Headache

• Nausea

• Back pain

• Stuffy nose

• Runny nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes.

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Severe dizziness

• Passing out

• Vision changes

• Blindness

• Hearing loss

• Hearing impairment

• Noise or ringing in the ears

• Erection that lasts more than 4 hours

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Coadministration with nitrates (either regularly and/or intermittently), nitric oxide donors, or guanylate cyclase stimulators (eg, riociguat).

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to vardenafil or any component of the formulation; concomitant use with cobicistat, indinavir, ritonavir, saquinavir, atazanavir, ketoconazole or itraconazole (Levitra, Staxyn), and erythromycin or clarithromycin (Staxyn); prior episode of non-arteritic anterior ischemic optic neuropathy.

Warnings/Precautions

Concerns related to adverse effects:

• Color discrimination: May cause dose-related impairment of color discrimination. Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterases (no safety information available).

• Hearing loss: Sudden decrease or loss of hearing has been reported rarely; hearing changes may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined.

• Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis or hypertrophic cardiomyopathy [HCM] with outflow tract obstruction); may be more sensitive to hypotensive actions. Concurrent use with alpha-adrenergic antagonist therapy may cause symptomatic hypotension; patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose. Avoid or limit concurrent substantial ethanol consumption as this may increase the risk of symptomatic hypotension.

• Priapism: Painful erection >6 hours in duration has been reported (rarely). Instruct patients to seek immediate medical attention if erection persists >4 hours. Use with caution in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia).

• Vision loss: Vision loss may occur rarely and be a sign of NAION. Instruct patients to seek medical assistance for sudden loss of vision in one or both eyes. Patients who have already experienced NAION are at an increased risk of recurrence. Other risk factors for NAION include low cup-to-disc ratio (“crowded disc”), coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and >50 years of age. Use with caution in these patients only when the benefits outweigh the risks. Safety and efficacy were not studied in patients with known degenerative retinal disorders (eg, retinitis pigmentosa); use is not recommended.

Disease-related concerns:

• Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie disease).

• Bleeding disorders: Use with caution in patients with bleeding disorders; safety and efficacy have not been established.

• Cardiovascular disease: Use is not recommended in patients with hypotension (<90/50 mm Hg); uncontrolled hypertension (>170/100 mm Hg); unstable angina or angina during intercourse; life-threatening arrhythmias, stroke, or MI within the last 6 months; cardiac failure or coronary artery disease causing unstable angina. Safety and efficacy have not been studied in these patients. Use caution in patients with left ventricular outflow obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy with outflow tract obstruction). There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction.

• Congenital QT prolongation: Not recommended for use in patients with congenital QT prolongation.

• Hepatic impairment: Use with caution in patients with moderate hepatic impairment (Child-Pugh class B); dosage adjustment is needed. Safety and efficacy have not been studied in patients with severe hepatic impairment (Child-Pugh class C); therefore, use in these patients is not recommended. Per the manufacturer, the oral disintegrating tablet should not be used in patients with moderate-to-severe hepatic impairment.

• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; safety and efficacy have not been established.

• Renal impairment: Safety and efficacy have not been studied in patients with end-stage renal disease requiring dialysis, therefore, use in these patients is not recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Nitrates: Concomitant use with all forms of nitrates is contraindicated. If nitrate administration is medically necessary, it is not known when nitrates can be safely administered following the use of vardenafil; however, when a 20 mg (film-coated tablet) was administered 24 hours prior to a 0.4 mg sublingual dose of nitroglycerin, no changes in blood pressure or heart rate were detected.

Special populations:

• Elderly: Use with caution in the elderly; dosage reduction may be necessary.

Dosage form specific issues:

• Phenylalanine: Some products may contain phenylalanine.

• Sorbitol: Some products may contain sorbitol; do not use in patients with fructose intolerance.

Other warnings/precautions:

• Appropriate use: Potential underlying causes of erectile dysfunction should be evaluated prior to treatment.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

In adults ≥65 years of age, vardenafil plasma concentrations were higher than younger males (mean Cmax was 34% higher), therefore, initial dose should be lower than the usual adult dose, using film-coated tablet (Levitra). Since the elderly often have concomitant diseases, many of which may be contraindicated with the use of vardenafil, a thorough knowledge of disease and medications must be accessed.

Reproductive Considerations

No effects on sperm motility or morphology were observed in healthy males.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal studies; however, vardenafil is not indicated for use in women.

Breast-Feeding Considerations

It is not known if vardenafil is present in breast milk. Vardenafil is not indicated for use in women.

Adverse Reactions

>10%:

Cardiovascular: Flushing (8% to 11%)

Central nervous system: Headache (14% to 15%)

2% to 10%:

Central nervous system: Dizziness (2%)

Gastrointestinal: Dyspepsia (3% to 4%), nausea (2%)

Neuromuscular & skeletal: Back pain (2%), increased creatine phosphokinase (2%)

Respiratory: Rhinitis (9%), flu-like symptoms (3%), nasal congestion (3%), sinusitis (3%)

<2%, postmarketing, and/or case reports: Abdominal pain, abnormal hepatic function tests, allergic edema, anaphylaxis, angina pectoris, angioedema, arthralgia, auditory impairment, basal cell carcinoma (Loeb 2015), blurred vision, chest pain, chromatopsia, conjunctivitis, decreased visual acuity, diaphoresis, diarrhea, drowsiness, dysesthesia, dysphagia, dyspnea, ejaculatory disorder, epistaxis, erythema, esophagitis, eye discomfort, eye pain, facial edema, gastritis, gastroesophageal reflux disease, glaucoma, hearing loss, hypersensitivity reaction, hypertension, hypertonia, hypoesthesia, hypotension, increased gamma-glutamyl transferase, increased intraocular pressure, insomnia, ischemic heart disease, laryngeal edema, malignant melanoma (Loeb 2015), muscle cramps, myalgia, myocardial infarction, neck pain, anterior ischemic optic neuropathy (nonarteritic; NAION), ocular hyperemia, orthostatic hypotension, pain, palpitations, paresthesia, pharyngitis, photophobia, priapism, pruritus, retinal vein occlusion, seizure, skin photosensitivity, skin rash, sleep disorder, syncope, tachycardia, temporary amnesia (global), tinnitus, ventricular tachyarrhythmia, vertigo, vision color changes, vision loss (temporary or permanent), visual disturbance (including dim vision), visual field defect, vomiting, watery eyes, weakness, xerostomia

* See Cautions in AHFS Essentials for additional information.

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alcohol (Ethyl): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Alpha1-Blockers (Nonselective): Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Alpha1-Blockers (Nonselective). Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Risk D: Consider therapy modification

Alpha1-Blockers (Uroselective): May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Alprostadil: Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil. Risk X: Avoid combination

Amyl Nitrite: Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Amyl Nitrite. Risk X: Avoid combination

Blood Pressure Lowering Agents: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Phosphodiesterase 5 Inhibitors may increase the serum concentration of Bosentan. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 5 mg dose within a 24-hour period if combined with moderate CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and moderate CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 24-hour period if combined with strong CYP3A4 inhibitors. Avoid concomitant use of Staxyn (vardenafil) and strong CYP3A4 inhibitors. Combined use is contraindicated outside of the US. Exceptions: Itraconazole; Ketoconazole (Systemic); Ritonavir. Risk D: Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk X: Avoid combination

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Etravirine: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Itraconazole: May increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to 5 mg per 24 hours with itraconazole 200 mg/day and 2.5 mg per 24 hours with itraconazole 400 mg/day. Avoid concomitant use of Staxyn (vardenafil) and itraconazole. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

Ketoconazole (Systemic): May increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to 5 mg per 24 hours with ketoconazole 200 mg/day and 2.5 mg per 24 hours with ketoconazole 400 mg/day. Avoid concomitant use of Staxyn (vardenafil) and ketoconazole. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Lorcaserin (Withdrawn From US Market): May enhance the adverse/toxic effect of Phosphodiesterase 5 Inhibitors. Specifically, the risk of developing priapism may be increased. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk X: Avoid combination

Nitroprusside: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Nitroprusside. Risk X: Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the adverse/toxic effect of other Phosphodiesterase 5 Inhibitors. Risk X: Avoid combination

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Riociguat: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Riociguat. Risk X: Avoid combination

Ritonavir: May increase the serum concentration of Vardenafil. Management: Limit Levitra (vardenafil) dose to a single 2.5 mg dose within a 72-hour period if combined with ritonavir. Avoid concomitant use of Staxyn (vardenafil) and ritonavir. Combined use is contraindicated outside of the US. Risk D: Consider therapy modification

Sapropterin: May enhance the hypotensive effect of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of Phosphodiesterase 5 Inhibitors. Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Vasodilators (Organic Nitrates): Phosphodiesterase 5 Inhibitors may enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination

Food Interactions

High-fat meals decrease maximum serum concentration 18% to 50%. Serum concentrations/toxicity may be increased with grapefruit juice. Management: Do not take with a high-fat meal. Monitor for increased effects/toxicity with concomitant grapefruit consumption.

Genes of Interest

• Cytochrome P450 3A4

Monitoring Parameters

Monitor for response, adverse reactions, blood pressure, and heart rate.

Advanced Practitioners Physical Assessment/Monitoring

Obtain baseline liver function tests; dosage adjustment may be needed. Obtain blood pressure and heart rate. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Educate patients using for impotence to report prolonged erection (>4 hours) or priapism.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor blood pressure and heart rate. Educate patients using for impotence to report prolonged erection (>4 hours) or priapism. Instruct patients to report any vision or hearing changes.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Levitra: 2.5 mg [DSC], 5 mg [DSC], 10 mg, 20 mg

Generic: 2.5 mg, 5 mg, 10 mg, 20 mg

Tablet Disintegrating, Oral:

Staxyn: 10 mg [contains aspartame; peppermint flavor]

Generic: 10 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Levitra: 5 mg, 10 mg, 20 mg

Generic: 5 mg, 10 mg, 20 mg

Tablet Disintegrating, Oral:

Staxyn: 10 mg [contains aspartame]

Generic: 10 mg

Anatomic Therapeutic Chemical (ATC) Classification

• G04BE09

Generic Available (US)

Yes

Pricing: US

Tablet, orally-disintegrating (Staxyn Oral)

10 mg (per each): $38.60

Tablet, orally-disintegrating (Vardenafil HCl Oral)

10 mg (per each): $36.18

Tablets (Levitra Oral)

10 mg (per each): $61.81

20 mg (per each): $61.81

Tablets (Vardenafil HCl Oral)

2.5 mg (per each): $55.56 - $58.72

5 mg (per each): $55.56 - $58.72

10 mg (per each): $55.56 - $58.72

20 mg (per each): $55.56 - $58.72

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Does not directly cause penile erections, but affects the response to sexual stimulation. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation and inflow of blood to the corpus cavernosum. Vardenafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE-5), which is responsible for degradation of cGMP in the corpus cavernosum; when sexual stimulation causes local release of NO, inhibition of PDE-5 by vardenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum; at recommended doses, it has no effect in the absence of sexual stimulation.

Pharmacodynamics/Kinetics

Onset of action: ~60 minutes

Absorption: Rapid

Distribution: Vd: 208 L

Protein binding: ~95% (parent drug and metabolite)

Metabolism: Hepatic via CYP3A4 (major), CYP2C and 3A5 (minor); forms metabolite (active)

Bioavailability: ~15%

Film-coated tablet: Elderly (≥65 years): AUC increased by 52%; Hepatic impairment (moderate, Child-Pugh class B): AUC increased by 160%

Oral disintegrating tablet: Elderly (≥65 years): AUC increased by 21% more compared to film-coated tablet. When administered with water, AUC decreases by 29%.

Half-life elimination: Terminal: Vardenafil and metabolite: 4 to 6 hours

Time to peak, plasma: 0.5 to 2 hours

Excretion: Feces (~91% to 95% as metabolites); urine (~2% to 6%)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: The AUC was 20% to 30% higher in moderate (CrCl 30 to 50 mL/minute) and severe (CrCl <30 mL/minute) renal impairment.

Hepatic function impairment: In patients with mild hepatic impairment (Child-Pugh class A), Cmax and AUC increased by 22% and 17%, respectively. In patients with moderate hepatic impairment (Child-Pugh class B), Cmax and AUC increased by 130% and 160%, respectively.

Geriatric: In men ≥65 years of age, the Cmax and AUC are increased 34% and 52%, respectively, for Levitra and by 21% and 39%, respectively, for Staxyn compared with men <45 years.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Vardenafil HCl; Vardenafil Hydrochloride

FDA Approval Date

August 19, 2003

References

Anderson JL, Adams CD, Antman EM, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(23):e663-e828. doi: 10.1161/CIR.0b013e31828478ac.[PubMed 23630129]10.1161/CIR.0b013e31828478ac

Caglayan E, Axmann S, Hellmich M, Moinzadeh P, Rosenkranz S. Vardenafil for the treatment of Raynaud phenomenon: a randomized, double-blind, placebo-controlled crossover study. Arch Intern Med. 2012;172(15):1182-1184.[PubMed 22710940]

Caglayan E, Huntgeburth M, Karasch T, et al. Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud disease. Arch Intern Med. 2006;166(2):231-233.[PubMed 16432094]

Cheitlin MD, Hutter AM Jr, Brindis RG, et al, “Use of Sildenafil (Viagra®) in Patients With Cardiovascular Disease,” J Am Coll Cardiol, 1999, 33(1):273-82.[PubMed 9935041]

Jackson G, Rosen RC, Kloner RA, et al, “The Second Princeton Consensus on Sexual Dysfunction and Cardiac Risk: New Guidelines for Sexual Medicine,” J Sex Med, 2006, 3(1):28-36.[PubMed 16409215]

Jing ZC, Yu ZX, Shen JY, et al; Efficacy and Safety of Vardenafil in the Treatment of Pulmonary Arterial Hypertension (EVALUATION) Study Group. Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2011;183(12):1723-1729. doi:10.1164/rccm.201101-0093OC[PubMed 21471085]

Kowal-Bielecka O, Fransen J, Avouac J, et al; EUSTAR Coauthors. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327-1339. doi:10.1136/annrheumdis-2016-209909[PubMed 27941129]

Levitra (vardenafil) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; August 2017.

Levitra (vardenafil) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; February 2020.

Loeb S, Folkvaljon Y, Lambe M, et al. Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma. JAMA. 2015;313(24):2449-2455.[PubMed 26103029]

McVary KT, “Clinical Practice. Erectile Dysfunction,” N Engl J Med, 2007, 357(24):2472-81.[PubMed 18077811]

Nehra A, Jackson G, Miner M, et al. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc. 2012;87(8):766-778. doi: 10.1016/j.mayocp.2012.06.015.[PubMed 22862865]10.1016/j.mayocp.2012.06.015

O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2013;128(25):e481.] Circulation. 2013;127(4):e362-e425.[PubMed 23247304]

Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomized trials. Ann Rheum Dis. 2013;72(10):1696-1699.[PubMed 23426043]

Staxyn (vardenafil) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; August 2017.

Staxyn (vardenafil) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; February 2020.

Brand Names: International

Levitra (AE, AR, AT, AU, BB, BE, BG, BH, BM, BR, BS, BZ, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DO, EC, EE, EG, ES, ET, FI, FR, GB, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IT, JM, JO, JP, KR, KW, LB, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PR, PT, QA, RO, RU, SA, SE, SG, SI, SK, SR, SV, TH, TR, TT, TW, UA, VE, VN); Levitra ODT (BH, EC, HK, JO, KR, TZ); Levitra Orodispersible (CY, IL); Powerecta (EG); Romantigra (EG); Valenty (BD); Vardena (EG); Vivanza (BG, ES, IE, MT); Yaila (KR)

Last Updated 5/2/20