Elsaad products
Member Login


Newsletter
 
 
New Products
Product Name
:
TIGER MAN
Chemical Name
:
Vardenafil
Therapeutic Category
:
Urinary tract drugs
Pharmacologic Category
:
Phosphodiesterase-5 Enzyme Inhibitor
Pharmaceutical Form
:
Tablets
Composition
:
Vardenafil Hydrochloride 2.5mg / 5mg /10mg /20mg
Dosing
 
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: 10 mg 60 minutes prior to sexual activity; dosing range: 5-20 mg; to be given as one single dose and not given more than once daily


Dosing: Geriatric

Erectile dysfunction: Elderly ≥65 years: Oral: Initial: 5 mg 60 minutes prior to sexual activity; to be given as one single dose and not given more than once daily.


Dosing: Renal Impairment

Dose adjustment not needed for mild, moderate, or severe impairment; use not recommended in patients on hemodialysis.


Dosing: Hepatic Impairment

Child-Pugh class A: No adjustment required

Child-Pugh class B:

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

Use
 
Treatment of erectile dysfunction (ED)
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%), CPK increased (2%)

Respiratory: Rhinitis (9%), nasal congestion (3%), sinusitis (3%)

Miscellaneous: Flu-like syndrome (3%)

<2% (Limited to important or life-threatening): Abnormal ejaculation, amnesia (transient global), anaphylactic reaction, angina, angioedema, arthralgia, dyspnea, hearing decreased, hearing loss, hyper-/hypotension, insomnia, liver function tests abnormal, MI, myalgia, nonarteritic ischemic optic neuropathy (NAION), orthostatic hypotension, pain, photophobia, photosensitivity, priapism, pruritus, rash, somnolence, syncope, tachycardia, tinnitus, ventricular tachyarrhythmia, vertigo, vision abnormal, visual acuity reduced, visual field defects, vision loss (temporary or permanent)

Contraindications
 

Hypersensitivity to vardenafil or any component of the formulation; concurrent (regular or intermittent) use of organic nitrates in any form (eg, nitroglycerin, isosorbide dinitrate)

Warnings / Precautions Drug
 

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 obstructive cardiomyopathy); 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: Has been reported (rarely) with use. 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 nonarteritic anterior ischemic optic neuropathy (NAION). Risk may be increased with history of vision loss. 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. 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's 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). 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:

• Alpha-blockers: Use with caution in patients taking alpha-blockers; may cause hypotension. Safety of this combination may be affected by other antihypertensives and intravascular volume depletion. Patients should be hemodynamically stable prior to initiating therapy. Initiate vardenafil at the lowest recommended dose.

• Drugs with QT prolongation potential: Use with caution in patients taking medications known to prolong the QT interval. Avoid use in patients taking Class Ia or III antiarrhythmics.

• High potential for interactions: Use film-coated tablet with caution in patients taking strong CYP3A4 inhibitors (see Drug Interactions); dosage reductions may be necessary; consider alternative agents that avoid or lessen the potential for CYP-mediated interactions. Avoid use of the oral disintegrating tablet with moderate-to-strong CYP3A4 inhibitors.

• 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; the ACC/AHA 2007 guidelines support administration of nitrates only if 24 hours have elapsed.

• Other treatments for erectile dysfunction: Safety and efficacy with other treatments for erectile dysfunction have not been established; concurrent use is not recommended.

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.

Interactions
 

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

Alpha1-Blockers: Phosphodiesterase 5 Inhibitors may enhance the hypotensive effect of Alpha1-Blockers. 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

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

Antihypertensives: Phosphodiesterase 5 Inhibitors may enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Boceprevir: May increase the serum concentration of Vardenafil. Management: Limit vardenafil maximum dose to 2.5 mg every 24 hours and monitor closely for symptoms of vardenafil toxicity (including hypotension, visual changes, syncope, and priapism) during treatment with boceprevir. Risk D: Consider therapy modification

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

Clarithromycin: May increase the serum concentration of Vardenafil. Management: Recommendations regarding the concomitant use of vardenafil with clarithromycin vary between international labelings and between commercially available vardenafil brand name products (Levitra, Staxyn). Consult appropriate product labelings. Risk D: Consider therapy modification

Cobicistat: May increase the serum concentration of Vardenafil. Management: Recommendations regarding use of vardenafil with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate product vary based on specific vardenafil brand and/or international labeling. Consult appropriate product labeling. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra, Staxyn) or by international labeling. Consult appropriate product labeling for specific recommendations. Risk D: Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Erythromycin (Systemic): May increase the serum concentration of Vardenafil. Management: Limit dose of vardenafil film-coated tablets (Levitra) to 5 mg per 24 hours with concomitant use of erythromycin. Concomitant use of vardenafil orally disintegrating tablets (Staxyn) with erythromycin is not recommended. Risk D: Consider therapy modification

Etravirine: May decrease the serum concentration of Phosphodiesterase 5 Inhibitors. Management: No empiric dosage adjustments are recommended with concomitant therapy; however, dose of the phosphodiesterase inhibitor may need to be altered based on clinical response. Risk C: Monitor therapy

Fluconazole: May increase the serum concentration of Vardenafil. Management: Limit vardenafil doses to a maximum of 5 mg per 24-hour period in patients receiving concurrent therapy with a moderate CYP3A4 inhibitor such as fluconazole. Risk D: Consider therapy modification

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Risk D: Consider therapy modification

Itraconazole: May increase the serum concentration of Vardenafil. Management: Limit vardenafil dosing to a maximum of 5 mg per 24 hours in patients receiving itraconazole 200 mg/day, and a maximum of 2.5 mg per 24 hours in patients receiving itraconazole 400 mg/day. Risk D: Consider therapy modification

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Ketoconazole (Systemic): May increase the serum concentration of Vardenafil. Management: Limit vardenafil dosing to a maximum of 5 mg per 24 hours in patients receiving ketoconazole 200 mg/day, and a maximum of 2.5 mg per 24 hours in patients receiving ketoconazole 400 mg/day. Risk D: Consider therapy modification

Lorcaserin: 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. 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

Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Risk D: Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Risk C: Monitor therapy

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

Posaconazole: May increase the serum concentration of Vardenafil. Management: Limit vardenafil dosing to a maximum of 2.5 mg per 24 hours in patients receiving concurrent therapy with strong CYP3A4 inhibitors, such as posaconazole. Risk D: Consider therapy modification

Protease Inhibitors: May increase the serum concentration of Vardenafil. Management: Limit vardenafil adult dose to max of 2.5 mg/72 hrs with ritonavir, atazanavir, or darunavir; limit to max adult dose of 2.5 mg/24 hrs with other protease inhibitors. Risk D: Consider therapy modification

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

Telaprevir: May increase the serum concentration of Vardenafil. Management: In patients receiving telaprevir, vardenafil dosing should be limited to 2.5 mg per 72-hour period with close monitoring for signs/symptoms of vardenafil toxicity (including hypotension, visual changes, syncope, and priapism). Risk D: Consider therapy modification

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

Voriconazole: May increase the serum concentration of Vardenafil. Management: Limit vardenafil dosing to a maximum of 2.5 mg per 24 hours in patients receiving concurrent therapy with strong CYP3A4 inhibitors, such as voriconazole. Risk D: Consider therapy modification

Pregnancy
 
Pregnancy Risk Factor

B

Pregnancy Implications

Teratogenic effects were not observed in animal studies; however, vardenafil is not indicated for use in women. No effects on sperm motility or morphology were observed in healthy males.

Lactation
 

Excretion in breast milk unknown/not indicated for use in women.

Monitoring Parameters
 
Monitor for response, adverse reactions, blood pressure, and heart rate.
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: V d : 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%

Half-life elimination: Terminal: Vardenafil and metabolite: 3-6 hours

Time to peak, plasma: 0.5-2 hours

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

 
   
 
Powered by: TSS-EST.COM