Valenty

Approved Indications:

• Erectile Dysfunction (ED):
  Indicated for the treatment of erectile dysfunction in adult males, regardless of severity, including those with comorbid conditions such as diabetes mellitus, hypertension, and dyslipidemia.

Clinically Accepted Off-label Uses:

• Premature Ejaculation (PE):
  Sometimes used in combination with SSRIs or alone to enhance ejaculatory control.
• Pulmonary Arterial Hypertension (PAH):
  Investigated off-label for pulmonary hypertension due to its vasodilatory effects, though not a first-line therapy.
• Raynaud's Phenomenon:
  Considered for severe cases unresponsive to standard vasodilators.

Adult Males (18–64 years):

• Initial dose: 10 mg orally, taken approximately 60 minutes before sexual activity.
• Maintenance dose: Adjust based on efficacy and tolerability to 5 mg or 20 mg once daily as needed.
• Maximum frequency: Once per day.
• With or without food: High-fat meals may delay the onset.

Elderly (≥65 years):

• Start with 5 mg due to potential increased drug exposure.

Hepatic Impairment:

• Mild (Child-Pugh A): No dose adjustment required.
• Moderate (Child-Pugh B): Start with 5 mg; titrate with caution.
• Severe (Child-Pugh C): Use is not recommended.

Renal Impairment:

• Mild to moderate: No adjustment needed.
• Severe (CrCl <30 mL/min): Use with caution; max dose 5 mg.
• Dialysis: Use not studied; avoid.

Pediatric Use:
Not indicated for use in children or adolescents.

Administration Route:
Oral tablets or orally disintegrating tablets.

Vardenafil is a selective phosphodiesterase type 5 (PDE5) inhibitor. During sexual stimulation, nitric oxide (NO) is released in the corpus cavernosum of the penis, stimulating guanylate cyclase and increasing cyclic guanosine monophosphate (cGMP). Elevated cGMP causes smooth muscle relaxation and enhanced blood flow. Vardenafil prevents the breakdown of cGMP by inhibiting PDE5, thereby prolonging erection. Its effects are penis-specific due to localized PDE5 expression.

• Absorption: Rapidly absorbed; Tmax = ~0.7–1.0 hour. High-fat meals delay Tmax.
• Bioavailability: Approximately 15% (low due to first-pass metabolism).
• Distribution: Protein binding ~95%; volume of distribution ~208 L.
• Metabolism: Primarily hepatic via CYP3A4, with minor roles of CYP3A5 and CYP2C isoenzymes.
• Active Metabolites: M1 (with 28% potency of parent).
• Elimination Half-life: ~4–5 hours.
• Excretion: ~91–95% via feces; ~2–6% in urine.

• Pregnancy:
  Not indicated for use in women. Animal studies show no teratogenicity, but human data are insufficient. Classified as Category B (based on older FDA system) in some sources.
• Lactation:
  Not for use in nursing mothers. Unknown if excreted into breast milk. Use not recommended.
• Note: This drug is not intended for female use.

• Primary Class: Phosphodiesterase type 5 (PDE5) inhibitor
• Subclass: Second-generation PDE5 inhibitor (more selective than sildenafil)
• Related Drugs: Sildenafil, Tadalafil, Avanafil

• Known hypersensitivity to vardenafil or its components
• Concomitant use with nitrates (e.g., nitroglycerin, isosorbide dinitrate)
• Use with guanylate cyclase stimulators (e.g., riociguat)
• Patients with severe hepatic impairment (Child-Pugh Class C)
• Individuals with recent stroke, myocardial infarction, or unstable angina
• Severe hypotension (BP <90/50 mmHg)
• Hereditary degenerative retinal disorders (e.g., retinitis pigmentosa)
• Use with strong CYP3A4 inhibitors (e.g., ketoconazole >200 mg, ritonavir)

• Cardiovascular Risk: Use caution in patients with cardiovascular disease; sexual activity itself may pose a risk.
• Priapism: Erection lasting >4 hours requires urgent medical attention.
• Visual Disturbances: Rare cases of NAION (non-arteritic anterior ischemic optic neuropathy).
• Hearing Loss: Sudden hearing impairment has been reported.
• QT Prolongation: Avoid use with other drugs that prolong the QT interval.
• Hepatic/Renal Impairment: Adjust dose; use caution due to altered metabolism.
• Interaction with Alpha-blockers: May cause symptomatic hypotension.

Common:

• Headache
• Flushing
• Nasal congestion
• Dyspepsia
• Dizziness
• Nausea

Occasional:

• Visual changes (e.g., color vision disturbances)
• Back pain
• Muscle aches

Rare but Serious:

• Priapism
• NAION (sudden vision loss)
• Sudden hearing loss
• Seizures
• Cardiac events (e.g., MI, stroke)
• QT interval prolongation

Severity & Onset:
Typically dose-dependent; onset within 1 hour of dosing; serious events are rare but can occur suddenly.

Major Interactions:

• Nitrates: Life-threatening hypotension
• Guanylate cyclase stimulators (e.g., riociguat): Additive hypotension
• Strong CYP3A4 inhibitors: (e.g., ketoconazole, ritonavir) → increased plasma levels; contraindicated
• Moderate CYP3A4 inhibitors (e.g., erythromycin) → use lower vardenafil dose
• Alpha-blockers: Risk of symptomatic hypotension; separate doses by several hours

Minor Interactions:

• Alcohol: Enhanced vasodilation, hypotension
• Grapefruit juice: CYP3A4 inhibition → increases vardenafil levels

Metabolism:
Via CYP3A4 (major), CYP3A5, and CYP2C (minor)

• QT prolongation warning emphasized in revised FDA and EMA labeling.
• Orally disintegrating tablet (ODT) formulations approved for patients with swallowing difficulty.
• Ongoing studies are evaluating daily low-dose regimens for chronic ED and investigational use in PE.
• Combination therapy with SSRIs for PE is under clinical research.

• Temperature: Store below 25°C (77°F)
• Humidity: Keep in dry place; avoid humidity
• Light: Protect from direct light exposure
• Handling: Store in original packaging; keep out of reach of children
• Orally disintegrating tablets (ODT): Do not remove from blister until use; do not store split tablets
• Reconstitution/Refrigeration: Not applicable