Vardenafil is a medication primarily used to treat erectile dysfunction (ED) in men. It belongs to a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors, which work by increasing blood flow to the penis during sexual stimulation, thus facilitating an erection. Vardenafil is sold under the brand name Levitra among others.

Levitra does not directly cause penile erections but affects the response to sexual stimulation.

It is used to treat erectile dysfunction. It is also used (as off-label medicine) in adults for the treatment of Raynaud's phenomenon.

Vardenafil Dose in Adult

• it's important to remember that if you need a dose other than 10 mg, you should use film-coated tablets, not oral disintegrating tablets.

Vardenafil Dosage in the treatment of Erectile dysfunction:

Film-coated tablet (Levitra):

• For the film-coated tablet, such as Levitra, the typical dose is 10 mg taken orally about 60 minutes before sexual activity.
• The dose can range from 5 to 20 mg but should be taken as a single dose and not more than once a day, with a maximum of 20 mg daily.

The orally disintegrating tablet (Staxyn):

• For the oral disintegrating tablet, like Staxyn, the usual dose is also 10 mg taken orally around 60 minutes before sexual activity, with a maximum of 10 mg per day.
• It's crucial to adhere to your doctor's instructions and not exceed the recommended dosage to minimize the risk of side effects.

Vardenafil off label dosage in the treatment of Raynaud phenomenon:  

• Vardenafil is typically prescribed at a dose of 10 mg orally twice daily.
• Clinical trials have shown that this regimen can be effective in managing symptoms associated with Raynaud phenomenon.
• The treatment period in these trials lasted up to 6 weeks.

Vardenafil Dosing adjustment with other medications:

• Alpha-blocker (dose stable at vardenafil initiation):
  • Film-coated tablet (Levitra): Start with 5 mg vardenafil once daily; if adding an alpha-blocker, begin with the smallest dose possible and adjust carefully.
  • Oral disintegrating tablet (Staxyn): Don't start therapy with Staxyn. Begin with film-coated tablets at lower doses. Patients previously on film-coated tablets may switch to Staxyn as directed by their healthcare provider. Consider a time gap between doses (e.g., 6-hour interval) when coadministering.
• CYP3A4 Inhibitors:
  • Film-coated tablet (Levitra): Adjust vardenafil dosage when using potent CYP3A4 inhibitors (e.g., ritonavir, itraconazole).
    • For ritonavir, do not exceed a single dose of 2.5 mg vardenafil in 72 hours.
    • For indinavir, saquinavir, atazanavir, ketoconazole 400 mg, itraconazole 400 mg, and clarithromycin, limit to a single dose of 2.5 mg vardenafil in 24 hours.
    • For ketoconazole 200 mg, itraconazole 200 mg, and erythromycin, do not exceed a single dose of 5 mg vardenafil in 24 hours.
  • Oral disintegrating tablet (Staxyn): Avoid concurrent use with potent or moderate CYP3A4 inhibitors (e.g., ritonavir, ketoconazole).

Vardenafil Dose in Children

Not recommended in children 

Pregnancy Risk Factor B

• Vardenafil has been classified as Pregnancy Risk Factor B, indicating no adverse effects observed in animal studies, but it's not meant for use in women.
• While there were no adverse events in animal studies, it's important to note that vardenafil is not recommended for women.
• Additionally, in healthy males, no effects on sperm motility or morphology were seen.

Vardenafil can be used during breastfeeding

• It's uncertain whether vardenafil is present in breast milk, and because vardenafil isn't recommended for women, the potential effects on infants through breastfeeding haven't been studied.

Vardenafil Dose in Kidney disease:

• In patient with mild, moderate, or severe impairment kidney problem, no adjustment in dosage is necessary when taking vardenafil.
• For those undergoing hemodialysis, it's not recommended to use vardenafil.

Vardenafil Dose in Liver Disease:

• In patient with mild hepatic impairment (Child-Pugh class A), no adjustment in dosage is needed when taking vardenafil.
• Moderate hepatic impairment (Child-Pugh class B):
  • For the film-coated tablet (Levitra), the initial dose is 5 mg taken approximately 60 minutes before sexual activity, with a maximum daily dose of 10 mg. It should be taken as a single dose and not more than once daily.
  • Oral disintegrating tablets (Staxyn) are not recommended for use in this group.
• For severe hepatic impairment (Child-Pugh class C), the use of vardenafil is not recommended as it has not been studied in this population.

Common Side Effects of Vardenafil Include:

• Cardiovascular:
  • Flushing
• Central nervous system:
  • Headache

Less Common Side Effects of Vardenafil Include:

• Central Nervous System:
  • Dizziness
• Gastrointestinal:
  • Dyspepsia
  • Nausea
• Neuromuscular & Skeletal:
  • Back Pain
  • Increased Creatine Phosphokinase
• Respiratory:
  • Rhinitis
  • Flu-Like Symptoms
  • Nasal Congestion
  • Sinusitis

Contraindications to Vardenafil Include:

• When taking vardenafil, it's crucial to avoid coadministration with nitrates (either regularly or intermittently), nitric oxide donors, or guanylate cyclase stimulators like riociguat, as it can lead to severe hypotension.
• In Canadian labeling, additional contraindications not found in US labeling include hypersensitivity to vardenafil or any component of the formulation, concomitant use with certain medications such as indinavir, ritonavir, ketoconazole, or itraconazole (for Levitra and Staxyn), as well as erythromycin or clarithromycin (for Staxyn).
• It's also contraindicated if there's been a prior episode of nonarteritic anterior ischemic optic neuropathy (NAION).
• These precautions are essential to ensure safe usage and minimize potential risks.

Warnings and precautions

Color discrimination:

• When taking vardenafil, it's important to be aware that it may cause dose-related impairment of color discrimination.
• This means that it could affect how well you can distinguish between colors, especially at higher doses.
• Individuals with retinitis pigmentosa, a condition affecting the eyes, should use caution when taking vardenafil because a small number of them may have genetic disorders related to retinal phosphodiesterases.

Hearing loss:

• Sudden decrease or loss of hearing has been reported rarely with vardenafil use.
• Changes in hearing may also be accompanied by symptoms like ringing in the ears (tinnitus) and dizziness.
• However, it's important to note that a direct relationship between vardenafil therapy and hearing loss has not been firmly established.

Hypotension

• Vardenafil can lead to decreases in blood pressure due to its vasodilator effects, so it should be used cautiously in patients with conditions like left ventricular outflow obstruction (such as aortic stenosis or hypertrophic cardiomyopathy with outflow tract obstruction), as they may be more sensitive to its hypotensive actions.
• When vardenafil is used alongside alpha-adrenergic antagonist therapy, it may result in symptomatic hypotension, so patients need to be hemodynamically stable before starting treatment, usually at the lowest possible dose.
• It's advisable to avoid or limit substantial alcohol consumption as this can increase the risk of symptomatic hypotension.

Priapism

• Priapism, a prolonged and painful erection lasting more than six hours, has been reported rarely with vardenafil use.
• Patients should be instructed to seek immediate medical attention if an erection persists for more than four hours.
• It's important to exercise caution when using vardenafil in patients who have conditions that may predispose them to priapism, such as sickle cell anemia, multiple myeloma, or leukemia.
• Prompt medical attention is necessary to prevent potential complications associated with priapism.

Vision loss:

• Vision loss, although rare, can occur with vardenafil use and may indicate a condition called nonarteritic anterior ischemic optic neuropathy (NAION).
• Patients should be advised to seek medical help immediately if they experience sudden vision loss in one or both eyes while taking vardenafil.
• Those who have already had NAION are at higher risk of recurrence.
• Other risk factors for NAION include certain eye conditions like a low cup-to-disc ratio ("crowded disc"), as well as medical conditions such as coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and being over 50 years old.
• Vardenafil should be used cautiously in patients with these risk factors, with careful consideration of whether the benefits outweigh the risks.
• It's important to note that safety and efficacy of vardenafil have not been studied in patients with known degenerative retinal disorders like retinitis pigmentosa, and its use is not recommended in this population.

Anatomical penis deformation:

• Vardenafil should be used cautiously in patients with anatomical deformations of the penis, such as angulation, cavernosal fibrosis, or Peyronie's disease.
• These conditions can increase the risk of complications or discomfort during erection.

Bleeding disorders:

• Patients with bleeding disorders should use vardenafil with caution, as the safety and efficacy of the medication have not been established in this population.

Cardiovascular disease

• Vardenafil use is not recommended in patients with certain cardiovascular conditions, including hypotension (blood pressure below 90/50 mm Hg), uncontrolled hypertension (blood pressure above 170/100 mm Hg), unstable angina, recent heart attack (within the last 6 months), life-threatening arrhythmias, stroke, or heart failure.
• Additionally, safety and efficacy have not been studied in these patients.
• Caution should also be exercised in patients with left ventricular outflow obstruction (such as aortic stenosis or hypertrophic cardiomyopathy with outflow tract obstruction).
• Given the inherent cardiac risks associated with sexual activity, physicians should consider the cardiovascular health of their patients before initiating treatment for erectile dysfunction with vardenafil or any other medication.

Congenital QT prolongation:

• Vardenafil is not recommended for use in patients with congenital QT prolongation.
• This condition involves an abnormal heart rhythm that can lead to serious complications, so it's crucial to avoid medications that could potentially worsen it.

Hepatic impairment

• Patients with moderate hepatic impairment (Child-Pugh class B) should use vardenafil with caution, as dosage adjustments may be necessary to ensure safe and effective treatment.
• However, safety and efficacy have not been studied in patients with severe hepatic impairment (Child-Pugh class C), so vardenafil is not recommended for use in these individuals.
• According to the manufacturer, the oral disintegrating tablet should not be used in patients with moderate-to-severe hepatic impairment.

Peptic ulcer disease:

• Patients with active peptic ulcer disease should use vardenafil with caution, as the safety and efficacy of the medication have not been established in this population.
• Peptic ulcer disease involves ulcers in the stomach or small intestine, and certain medications may exacerbate this condition or interfere with healing.

Renal impairment

• Safety and efficacy of vardenafil have not been studied in patients with end-stage renal disease requiring dialysis.
• Therefore, vardenafil is not recommended for use in these patients.

Vardenafil: Drug Interaction

Monitor:

• Response: Keep track of how well vardenafil is working for you, including its effectiveness in improving erectile dysfunction symptoms.
• Adverse Reactions: Watch out for any negative side effects you might experience while taking vardenafil, and report them to your healthcare provider.
• Blood Pressure: Monitor your blood pressure regularly, especially if you have cardiovascular concerns, to ensure it remains within a safe range.
• Heart Rate: Keep an eye on your heart rate to detect any abnormalities, particularly if you have a history of heart conditions.

How to administer Vardenafil?

• Timing: Vardenafil can be taken with or without food, about 60 minutes before sexual activity, for best results.
• Oral Disintegrating Tablet (Staxyn):
  • Keep the tablet in its blister pack until you're ready to take it.
  • With dry hands, place the tablet directly on your tongue.
  • Let the tablet dissolve on your tongue within seconds; avoid taking it with any liquid.
  • Do not crush, split, or chew the tablet.

Following these instructions helps ensure that vardenafil is taken correctly and optimizes its effectiveness while minimizing any potential risks.

Mechanism of action of Vardenafil:

• Vardenafil doesn't directly cause penile erections but enhances the body's response to sexual stimulation.
• When sexually stimulated, nitric oxide (NO) is released in the corpus cavernosum of the penis.
• This NO activates an enzyme called guanylate cyclase, leading to increased levels of cyclic guanosine monophosphate (cGMP), which causes smooth muscle relaxation and allows blood to flow into the corpus cavernosum, producing an erection.
• Vardenafil works by inhibiting phosphodiesterase type 5 (PDE-5), an enzyme responsible for breaking down cGMP in the corpus cavernosum.
• By inhibiting PDE-5, vardenafil allows cGMP levels to remain elevated, promoting smooth muscle relaxation and increased blood flow, ultimately leading to an erection when sexually stimulated.
• It's important to note that vardenafil has no effect in the absence of sexual stimulation, and its action depends on the release of NO during sexual arousal.

Onset of Action:

• Approximately 60 minutes after administration.

Absorption:

• Rapid absorption into the bloodstream.

Distribution:

• Vardenafil has a large volume of distribution (V) of approximately 208 liters.

Protein Binding:

• About 95% of vardenafil and its metabolite bind to proteins in the blood.

Metabolism:

• Primarily metabolized in the liver by the enzyme CYP3A4, with minor contributions from CYP2C and CYP3A5. It forms an active metabolite.

Bioavailability:

• Vardenafil has a bioavailability of approximately 15%. In specific populations:
  • Film-coated tablet: Elderly individuals (65 years and older) may experience a 52% increase in area under the curve (AUC) compared to younger adults. Moderate hepatic impairment (Child-Pugh class B) can lead to a 160% increase in AUC.
  • Oral disintegrating tablet: Elderly individuals may experience a 21% greater increase in AUC compared to the film-coated tablet. When taken with water, the AUC decreases by 29%.

Half-life Elimination:

• Terminal half-life for vardenafil and its metabolite is approximately 4 to 6 hours.

Time to Peak Plasma Concentration:

• Vardenafil reaches peak plasma concentration within 0.5 to 2 hours after administration.

Excretion:

• Vardenafil and its metabolites are primarily excreted in the feces (approximately 91% to 95%), with a smaller amount excreted in the urine (approximately 2% to 6%).

International Brands of Vardenafil:

• APO-Vardenafil
• JAMP-Vardenafil
• JAMP-Vardenafil ODT
• Levitra
• MYLAN-VARDENAFIL
• Staxyn
• Levitra
• Levitra ODT
• Levitra Orodispersible
• Powerecta
• Romantigra
• Valenty
• Vardena
• Vivanza
• Yaila

Vardenafil Brands in Pakistan:

Levitra (Verdenafil) is not available in Pakistan.