Vardenafil

Usage

• Vardenafil is prescribed for the treatment of erectile dysfunction (ED), also known as impotence, in adult men. Erectile dysfunction is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance.
• Pharmacological Classification: Phosphodiesterase-5 (PDE5) inhibitor.
• Mechanism of Action: Vardenafil enhances the effect of nitric oxide, a naturally occurring chemical in the body that relaxes smooth muscle in the penis, allowing increased blood flow and facilitating erection during sexual stimulation.

Alternate Names

• INN: Vardenafil
• Brand Names: Levitra, Staxyn (orally disintegrating tablet)

How It Works

• Pharmacodynamics: Vardenafil selectively inhibits PDE5, the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the penis. By inhibiting PDE5, vardenafil increases cGMP levels, leading to smooth muscle relaxation and increased blood flow into the penis, resulting in an erection upon sexual stimulation.
• Pharmacokinetics:
  • Absorption: Vardenafil is rapidly absorbed after oral administration, with peak plasma concentrations reached within 30-120 minutes. A high-fat meal may delay absorption.
  • Metabolism: Primarily metabolized in the liver by CYP3A4, with minor contributions from CYP2C isoforms.
  • Elimination: Excreted as metabolites predominantly in feces (approximately 91-95%) and to a lesser extent in urine (approximately 2-6%).
• Mode of Action: Vardenafil exerts its effect by binding to the catalytic site of PDE5, preventing it from breaking down cGMP. This leads to an accumulation of cGMP in the smooth muscle cells of the penis, causing relaxation and vasodilation, thereby increasing blood flow and facilitating erection. The drug does not initiate an erection; sexual stimulation is required.
• Elimination Pathways: Primarily hepatic metabolism via CYP3A4, followed by fecal excretion.

Dosage

Standard Dosage

Adults:

• Initial dose: 10 mg orally, approximately 25-60 minutes before sexual activity.
• Dose range: 5-20 mg, adjusted based on efficacy and tolerability.
• Maximum dose: 20 mg once per day.

Children:

• Vardenafil is not indicated for use in individuals below 18 years of age.

Special Cases:

• Elderly Patients (≥65 years): A starting dose of 5 mg is recommended. Dose adjustments should be made cautiously based on individual tolerability.
• Patients with Renal Impairment: No dose adjustment is required for mild to moderate impairment. For severe renal impairment (creatinine clearance <30 mL/min), a starting dose of 5 mg is recommended.
• Patients with Hepatic Dysfunction:
  • Mild impairment (Child-Pugh A): No dose adjustment necessary.
  • Moderate impairment (Child-Pugh B): Starting dose of 5 mg. Maximum dose of 10 mg. Orally disintegrating tablets (ODT) are not recommended.
  • Severe impairment (Child-Pugh C): Vardenafil is contraindicated.
• Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease, especially those for whom sexual activity is inadvisable. Dose adjustments may be needed for patients taking certain medications.

Clinical Use Cases

Vardenafil’s clinical use is specifically for erectile dysfunction. The listed clinical use cases are not relevant to Vardenafil. Its use is not indicated in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest.

Dosage Adjustments

• Dose modifications may be needed based on age, hepatic and renal function, concomitant medications (especially CYP3A4 inhibitors), and individual response to treatment.

Side Effects

Common Side Effects:

• Headache
• Flushing
• Nasal congestion
• Dyspepsia
• Back pain
• Dizziness

Rare but Serious Side Effects:

• Priapism (prolonged and painful erection)
• Sudden vision loss or changes in color vision
• Sudden hearing loss or ringing in the ears
• Severe allergic reactions (e.g., hives, difficulty breathing, swelling of face, lips, tongue, or throat)
• Cardiovascular events (e.g., myocardial infarction, stroke)

Long-Term Effects:

• Potential for long-term side effects with chronic use is not fully established. Monitoring for adverse events is recommended.

Adverse Drug Reactions (ADR):

• Clinically significant ADRs include priapism, sudden vision or hearing loss, and severe allergic reactions. These require immediate medical intervention.

Contraindications

• Co-administration with nitrates or nitric oxide donors.
• Co-administration with guanylate cyclase stimulators (e.g., riociguat).
• Severe hepatic impairment (Child-Pugh C).
• End-stage renal disease requiring dialysis.
• Known hereditary degenerative retinal disorders (e.g., retinitis pigmentosa).
• Hypersensitivity to vardenafil.

Drug Interactions

• CYP3A4 Inhibitors: Concomitant use of strong CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin, clarithromycin) requires dosage adjustments of vardenafil.
• Nitrates: Co-administration is contraindicated due to the risk of severe hypotension.
• Alpha-blockers: Concomitant use may lead to symptomatic hypotension. Dosage adjustments and/or time separation of doses may be necessary.
• Other Medications: Grapefruit juice may increase vardenafil levels. Concomitant use with other medications metabolized by CYP3A4 may require dosage adjustments.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (US FDA). Vardenafil is not indicated for use in women.
• Limited data available on use during pregnancy. Not recommended unless the potential benefit outweighs the risk.
• Breastfeeding: Vardenafil is excreted in rat milk. It is unknown whether vardenafil is excreted in human breast milk. Use is not recommended.

Drug Profile Summary

• Mechanism of Action: PDE5 inhibitor, increases cGMP levels in the corpus cavernosum, leading to smooth muscle relaxation and increased blood flow.
• Side Effects: Headache, flushing, nasal congestion, dyspepsia, back pain; rarely, priapism, vision or hearing loss, allergic reactions.
• Contraindications: Nitrates, guanylate cyclase stimulators, severe hepatic impairment, end-stage renal disease, retinitis pigmentosa.
• Drug Interactions: CYP3A4 inhibitors, nitrates, alpha-blockers, grapefruit juice.
• Pregnancy & Breastfeeding: Not recommended for use in women, limited data during pregnancy, unknown if excreted in human milk.
• Dosage: 10 mg initially (5 mg in elderly), adjustable 5-20 mg once daily.
• Monitoring Parameters: Blood pressure, vision and hearing changes, signs of allergic reactions.

Popular Combinations

Vardenafil is typically used as monotherapy. Combination therapy for ED is not commonly practiced, though other treatments for ED may be considered if Vardenafil is not effective or tolerated.

Precautions

• General Precautions: Cardiovascular assessment prior to initiation. Screen for contraindications and potential drug interactions. Caution in patients with conditions predisposing to priapism.
• Specific Populations: See “Dosage - Special Cases”.
• Lifestyle Considerations: Alcohol may exacerbate certain side effects like hypotension. Smoking may decrease the effectiveness of the medication. Dietary fat may delay absorption. Caution should be exercised when driving or operating machinery due to the potential for dizziness or vision changes.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Vardenafil?

A: The recommended starting dose is 10 mg taken approximately 25-60 minutes before sexual activity. The dose can be adjusted based on efficacy and side effects, ranging from 5 mg to a maximum of 20 mg per day. For elderly patients or those with hepatic or renal impairment, a lower starting dose may be recommended.

Q2: How does Vardenafil differ from other PDE5 inhibitors?

A: While all PDE5 inhibitors share a similar mechanism of action, they have slight differences in pharmacokinetic properties, such as onset and duration of action. Vardenafil’s onset of action is relatively rapid, typically within 30-60 minutes.

Q3: What are the most common side effects of Vardenafil?

A: The most common side effects include headache, flushing, nasal congestion, indigestion, and back pain. These are typically mild and transient.

Q4: Can Vardenafil be taken with food?

A: Yes, vardenafil can be taken with or without food. However, a high-fat meal may delay the onset of action.

Q5: What should I do if I experience a prolonged erection (priapism)?

A: Priapism is a rare but serious side effect. Seek immediate medical attention if an erection lasts longer than 4 hours.

Q6: Can Vardenafil be used by women?

A: No, vardenafil is not indicated for use in women.

Q7: Does Vardenafil interact with other medications?

A: Yes, vardenafil can interact with several medications, especially nitrates and CYP3A4 inhibitors. It is essential to inform your doctor about all medications you are taking, including over-the-counter drugs and supplements.

Q8: Can I take Vardenafil if I have heart problems?

A: Patients with certain heart conditions should use vardenafil with caution or avoid it altogether. Consult your doctor for advice if you have any cardiovascular issues.

Q9: Is Vardenafil safe for long-term use?

A: The long-term safety of vardenafil has not been fully evaluated. Regular monitoring is recommended for patients using it chronically.

Q10: What are the key contraindications for Vardenafil?

A: Vardenafil is contraindicated in patients taking nitrates or guanylate cyclase stimulators, those with severe hepatic impairment or end-stage renal disease, and those with hereditary degenerative retinal disorders.