Vardenafil

Vardenafil is a phosphodiesterase type 5 (PDE5) inhibitor used to treat erectile dysfunction (ED) in adult men. It is the active ingredient in the branded preparation Levitra and is also available as a generic medicine and as an orodispersible tablet formulation. Vardenafil is a well-established treatment for ED across a broad range of aetiologies, including psychogenic, vascular, diabetic, and post-prostatectomy causes.

How Vardenafil Works

Erection depends on the release of nitric oxide in the corpus cavernosum of the penis in response to sexual stimulation. Nitric oxide activates guanylate cyclase, increasing levels of cyclic guanosine monophosphate (cGMP), which relaxes smooth muscle in the arterial walls of the penis and allows blood to flow in to produce an erection. PDE5 is the enzyme responsible for breaking down cGMP, thereby ending the erection. Vardenafil selectively inhibits PDE5, allowing cGMP to accumulate, prolonging and sustaining smooth muscle relaxation and facilitating erection in response to sexual stimulation.

Crucially, vardenafil does not cause erections spontaneously, it only enhances the natural erectile response when sexual stimulation is present. Without arousal and the associated nitric oxide release, vardenafil has no meaningful clinical effect.

Potency and Selectivity

Vardenafil is highly selective for PDE5 compared to other PDE subtypes, which contributes to its efficacy and side effect profile. It is considered more potent than sildenafil at equivalent doses, with clinical activity observed at lower concentrations. The standard tablet formulation typically reaches peak plasma concentrations 30 to 60 minutes after ingestion, and the therapeutic window extends for approximately four to five hours. The orodispersible formulation may have a faster onset in some patients.

How to Take Vardenafil

Take vardenafil approximately 25 to 60 minutes before planned sexual activity. It may continue to be effective for up to five hours after taking it. Swallow standard film-coated tablets whole with a glass of water. Orodispersible tablets (which dissolve on the tongue) should be placed on the tongue and allowed to dissolve without water — do not swallow them whole.

Vardenafil can be taken with or without food. A high-fat meal may delay absorption and slow the onset of effect, so a light meal is preferable if you want faster action. Do not take more than one dose in 24 hours.

Dose

The usual starting dose is 10 mg. Depending on your response, this can be adjusted to 5 mg (if side effects are a problem) or 20 mg (if 10 mg is not sufficient). For older men or those with liver or kidney problems, a lower starting dose is usually recommended.

Standard starting dose: 10 mg taken 25-60 minutes before sexual activity. One tablet per 24-hour period only.

Dose adjustment: May be increased to 20 mg or reduced to 5 mg depending on individual response and tolerability.

Elderly patients (65 years and over): Starting dose of 5 mg is recommended, which may be increased to 10 mg if tolerated.

Hepatic impairment: Starting dose of 5 mg in moderate hepatic impairment (Child-Pugh B). Not recommended in severe hepatic impairment.

Renal impairment: No dose adjustment required for mild to moderate renal impairment. Caution is needed in severe impairment.

Concomitant CYP3A4 inhibitors: Dose reduction is required with moderate CYP3A4 inhibitors (e.g., erythromycin, clarithromycin) and vardenafil is contraindicated with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir).

Vardenafil is available as film-coated tablets of 5 mg, 10 mg, and 20 mg, and as 10 mg orodispersible tablets.

Common Side Effects

• Headache (the most commonly reported, related to vasodilation)
• Flushing of the face, neck, or chest
• Nasal congestion or runny nose
• Indigestion or heartburn
• Dizziness, particularly on standing up quickly

Important Warnings

Never take vardenafil with nitrate medicines (such as GTN spray, isosorbide mononitrate, or amyl nitrite) — this combination causes a severe and potentially life-threatening drop in blood pressure. Seek immediate medical attention if an erection lasts more than four hours (priapism), as this can permanently damage erectile tissue. Rare cases of sudden vision or hearing loss have been reported. If you experience any visual disturbance, chest pain, or severe dizziness during sexual activity, stop and seek medical attention.

Vardenafil carries several clinically important warnings, particularly regarding cardiovascular safety and drug interactions.

Nitrates and Cardiovascular Contraindications

Vardenafil must never be taken with nitrates in any form. This includes glyceryl trinitrate (GTN) tablets, sprays, and patches, as well as isosorbide mononitrate and dinitrate. Both nitrates and PDE5 inhibitors lower blood pressure through nitric oxide pathways, and their combination can cause a sudden, severe, and potentially life-threatening drop in blood pressure. Men who use nitrates for angina should not use vardenafil and should discuss alternative ED treatments with their doctor.

Sexual activity itself represents a moderate cardiovascular stress, equivalent to climbing two flights of stairs. Men with significant cardiovascular disease should undergo a cardiovascular risk assessment before starting any PDE5 inhibitor. Vardenafil is generally not recommended in men who have had a recent heart attack (within the past 90 days), men with unstable angina, men with severe heart failure, or those with blood pressure below 90/50 mmHg at rest.

QT Prolongation and Drug Interactions

Vardenafil prolongs the QT interval on the ECG, particularly at doses above 10 mg. It should not be used in combination with other medicines that prolong the QT interval (such as class Ia or III antiarrhythmics). This risk is increased in men with inherited long QT syndrome, hypokalaemia, or hypomagnesaemia. Vardenafil is metabolised by CYP3A4 and CYP3A5, making it subject to significant interactions with inhibitors of these enzymes; dose reductions or avoidance are required accordingly. Alpha-blockers used for prostate conditions or hypertension can also cause significant additive hypotension with vardenafil.

• Concurrent use of nitrates in any form (GTN, isosorbide mononitrate, isosorbide dinitrate, amyl nitrite/poppers)
• Concurrent use of strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, indinavir, atazanavir)
• Hypersensitivity to vardenafil or any excipient
• Severe hepatic impairment (Child-Pugh C)
• End-stage renal disease requiring dialysis
• Recent myocardial infarction within the past 90 days
• Unstable angina or angina occurring during sexual activity
• Heart failure (New York Heart Association class II or above with borderline low blood pressure)
• Resting blood pressure below 90/50 mmHg or above 170/100 mmHg
• Inherited degenerative retinal disorders such as retinitis pigmentosa
• Congenital or acquired QT prolongation
• Use of class Ia or class III antiarrhythmic medicines