Vardamate10 mg

Vardamate is a phosphodiesterase type 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED) in adult men. This is the sole FDA-approved and internationally recognized indication for Vardamate.

• Established/approved use: Treatment of erectile dysfunction, to help achieve and maintain an erection sufficient for satisfactory sexual activity, in response to sexual stimulation.

Vardamate is not indicated for use in women or children, and it does not increase sexual desire; it works only in the presence of sexual stimulation.

Each film-coated tablet contains Vardenafil (as hydrochloride trihydrate) 5 mg, 10 mg, or 20 mg. An orally disintegrating tablet formulation containing Vardenafil 10 mg is also available in some markets. Excipients vary by manufacturer and formulation.

Vardamate is a potent, selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the enzyme responsible for degradation of cGMP in the corpus cavernosum of the penis. By inhibiting PDE5, Vardamate enhances the effect of nitric oxide released during sexual stimulation, increasing cGMP levels, which results in smooth muscle relaxation and increased blood inflow to the penis, producing an erection.

Vardamate has no effect in the absence of sexual stimulation and belongs to the same pharmacological class as other PDE5 inhibitors used for erectile dysfunction.

Phosphodiesterase type 5 (PDE5) inhibitor; drug for erectile dysfunction

Mechanism of Action

Vardenafil selectively inhibits PDE5, the enzyme responsible for the breakdown of cGMP in the smooth muscle of the corpus cavernosum. Sexual stimulation triggers local release of nitric oxide, which activates guanylate cyclase, raising cGMP levels and causing smooth muscle relaxation and increased penile blood flow. By blocking cGMP degradation, Vardenafil potentiates this natural response, facilitating an erection only when sexual stimulation occurs.

Pharmacokinetics

• Absorption: Rapidly absorbed after oral administration; peak plasma concentration reached in about 30–120 minutes (median ~60 minutes); a high-fat meal delays absorption.
• Protein binding: Approximately 95% bound to plasma proteins.
• Metabolism: Extensively metabolized in the liver, primarily by the CYP3A4 enzyme (with minor contribution from CYP3A5 and CYP2C9), to an active metabolite with pharmacologic activity similar to the parent compound.
• Elimination half-life: Approximately 4–5 hours.
• Excretion: Mainly via feces (~91–95%) with a smaller portion excreted in urine (~2–6%).

Vardamate is metabolized mainly by CYP3A4, and clinically significant interactions can occur through this pathway or through additive vasodilatory/hypotensive effects.

• Organic nitrates (any form): Contraindicated. Concomitant use can cause severe, potentially fatal hypotension (see Contraindications).
• Guanylate cyclase (GC) stimulators (e.g., riociguat): Contraindicated due to additive hypotensive effects.
• Alpha-blockers (e.g., tamsulosin, doxazosin): Concomitant use may cause symptomatic hypotension (dizziness, syncope). Patients should be stable on alpha-blocker therapy before starting Vardamate, and Vardamate should generally be started at the lowest dose with appropriate spacing of doses.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, indinavir, clarithromycin, erythromycin): May significantly increase Vardamate plasma levels; dose limitation or avoidance is recommended per product labeling.
• Class IA and Class III antiarrhythmics (e.g., quinidine, procainamide, amiodarone, sotalol): Avoid concomitant use due to potential additive QT-interval prolongation.
• Other PDE5 inhibitors or ED therapies: Concomitant use is not recommended — no added efficacy benefit and increased risk of additive adverse effects.
• Other antihypertensive agents/alcohol: May have additive blood-pressure–lowering effects; use with caution.

Most adverse effects of Vardamate are mild to moderate and transient.

Common Side Effects

• Headache
• Flushing
• Nasal congestion/rhinitis
• Dyspepsia (indigestion)
• Dizziness
• Back pain
• Sinusitis
• Flu-like symptoms

Serious/Rare Side Effects (require prompt medical attention)

• Priapism: A prolonged, painful erection lasting more than 4 hours is a medical emergency and requires immediate treatment to prevent permanent damage to the penis.
• Sudden vision loss or decrease in one or both eyes, including reports of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition associated with PDE5 inhibitors as a class. Vardamate should be stopped immediately and medical care sought if this occurs.
• Sudden hearing loss or decrease, sometimes with tinnitus and dizziness, reported with PDE5 inhibitors including Vardamate. Discontinue and seek medical attention if this occurs.
• Cardiovascular events (chest pain, palpitations, or, rarely, myocardial infarction) during or after sexual activity in men with underlying cardiac risk factors.
• Prolonged QT interval (dose-related), rarely associated with serious arrhythmia.

Vardamate is indicated only for use in adult men and is not intended or approved for use in women; therefore, pregnancy and lactation considerations are not applicable to this medicine. Vardamate should never be taken by women, including women who are pregnant or breastfeeding.

Cardiovascular risk: Sexual activity carries a degree of cardiac risk; physicians should consider the cardiovascular status of patients before prescribing Vardamate, particularly those with a history of cardiac disease.

Hypotension with alpha-blockers: Concomitant use may cause symptomatic hypotension (see Interactions).

Nitrate contraindication: Never combine Vardamate with organic nitrates — see Contraindications for details, as this combination can be fatal.

Vision changes: Stop Vardamate and seek immediate medical attention if sudden decrease or loss of vision occurs in one or both eyes (possible NAION) — see Side Effects.

Hearing changes: Stop Vardamate and seek medical attention if sudden decrease or loss of hearing occurs, with or without tinnitus or dizziness.

Priapism: Seek emergency medical care for an erection lasting longer than 4 hours — see Side Effects.

QT prolongation: Use caution in patients with congenital long QT syndrome or those taking other QT-prolonging medications.

Anatomical deformity/predisposition to priapism: Use with caution in men with penile deformity (e.g., Peyronie's disease) or conditions predisposing to priapism (e.g., sickle cell disease, multiple myeloma, leukemia).

Bleeding disorders/active peptic ulcer: Use with caution as safety in these populations has not been established.

No protection against STIs: Vardamate does not protect against sexually transmitted infections; barrier protection should still be used as appropriate.

There is limited clinical experience with Vardamate overdose. Doses higher than those recommended may increase the incidence and severity of typical adverse effects such as headache, flushing, dizziness, dyspepsia, and hypotension. In case of suspected overdose, seek immediate medical attention or contact a poison control center; supportive symptomatic treatment should be provided by a physician as needed. There is no specific antidote for Vardamate overdose. Since Vardamate is highly protein-bound, dialysis is unlikely to be of significant benefit in overdose management.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly: Consider a starting dose of 5 mg in patients aged 65 years and older due to reduced clearance in this age group; monitor for increased sensitivity to side effects.

Hepatic impairment: No adjustment needed for mild impairment; reduced starting dose (5 mg, maximum 10 mg) recommended for moderate impairment; use is not recommended in severe hepatic impairment.

Renal impairment: No adjustment needed for mild-to-moderate impairment; a lower starting dose (5 mg) is recommended in severe renal impairment or patients on dialysis.

Women and children: Vardamate is not indicated for use in women or in pediatric patients; safety and efficacy in these populations have not been established (see Pregnancy and Lactation, and Pediatric Uses).

Phosphodiesterase type 5 (PDE5) inhibitors