Vardenafil was approved by the U.S. Food and Drug Administration (FDA) on August 19, 2003, for the treatment of ED. Vardenafil is a selective phosphodiesterase type 5 (PDE5) inhibitor used in the treatment of erectile dysfunction. As a phosphodiesterase-5 (PDE5) inhibitor, it works by increasing blood flow to the penis during sexual stimulation to help achieve and sustain an erection. It was co-developed and co-marketed by Bayer Pharmaceuticals, GlaxoSmithKline (GSK), and Schering-Plough.
BRAND NAMES
Levitra -is 10 mg, taken orally, as needed, approximately 60 minutes before sexual activity.
MECHANISM OF ACTION
Vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, works by enhancing blood flow to the penis during sexual stimulation, thereby treating erectile dysfunction. It works by inhibiting the enzyme PDE5, which prevents the breakdown of cyclic guanosine monophosphate (cGMP). By preserving cGMP levels, vardenafil enhances the natural erectile response by relaxing the smooth muscles and widening the blood vessels in the penis. The medication remains ineffective without sexual stimulation.
PHARMACOKINETICS
Absorption
Vardenafil is rapidly absorbed, with an absolute bioavailability of around 15%. However, the speed and peak concentration of its absorption are significantly affected by the formulation and the presence of food.
Distribution
The average steady-state volume of distribution for vardenafil is 208 litres.
Metabolism
Vardenafil is metabolized predominantly in the liver by the cytochrome P450 (CYP) enzyme system, specifically the CYP3A4 isoform, with lesser contributions from CYP3A5 and CYP2C isoforms. The metabolism produces several compounds, most notably a major active metabolite called N-desethyl vardenafil (M1).
Excretion
Vardenafil is mainly eliminated through feces, which accounts for 91–95% of its excretion, while just 2–6% is eliminated via the urine.
PHARMACODYNAMICS
Vardenafil is a highly potent and selective phosphodiesterase type 5 (PDE5) inhibitor that treats erectile dysfunction (ED). The pharmacodynamics of vardenafil describes how it interacts with the body on a molecular level to produce its therapeutic effects.
ADMINISTRATION
Vardenafil is available in two oral forms: a standard tablet and a rapidly disintegrating tablet that dissolves in the mouth and is swallowed without water. It is typically taken as needed, with or without food, about 60 minutes before sexual activity. It should generally not be used more than once every 24 hours.
DOSAGE AND STRENGTHS
Vardenafil is an oral medication available in two primary dosage forms: film-coated tablets and orally disintegrating tablets (ODTs). Vardenafil is offered in multiple strengths, including 2.5 mg, 5 mg, 10 mg, and 20 mg, with a maximum recommended dose of 20 mg per day.
DRUG INTERACTIONS
Vardenafil interacts with several medications, most notably nitrates and alpha-blockers, by causing a dangerous drop in blood pressure. Taking it with nitrates like nitroglycerin is strictly prohibited, as is co-administration with guanylate cyclase stimulators, such as riociguat. Additionally, certain drugs that inhibit the CYP3A4 enzyme in the liver, including some antibiotics can increase vardenafil levels in the blood and raise the risk of side effects. The consumption of grapefruit juice can also increase vardenafil concentrations, and combining vardenafil with other erectile dysfunction treatments is not recommended.
FOOD INTERACTIONS
Two main food interactions for vardenafil are grapefruit and high-fat meals. While vardenafil can be taken with or without food, understanding these interactions is key to managing its effectiveness and safety. Grapefruit and grapefruit juice pose the most significant food interaction with vardenafil, and should be completely avoided. Eating a high-fat meal may delay and decrease vardenafil absorption, which can slow its onset and reduce its overall effectiveness. While not a food, alcohol is a common consumption concern. Vardenafil and alcohol can both lower blood pressure, and consuming large amounts of alcohol with vardenafil can increase the risk of side effects.
CONTRAINDICATIONS
Vardenafil is contraindicated in individuals who take nitrate medications or guanylate cyclase (GC) stimulators due to the risk of a dangerous drop in blood pressure. Its use is also not recommended in patients with certain severe cardiovascular conditions and in those with specific hereditary eye disorders.
SIDE EFFECTS
Allergic reaction.
Severely low blood pressure.
Heart-related symptoms.
Sudden hearing loss.
Sudden vision loss.
Prolonged or painful erection.
Headache.
Stuffy or runny nose.
Back or muscle pain.
Upset stomach.
OVER DOSE
An overdose of vardenafil is an exaggeration of its normal effects and can lead to dangerous complications.
Severe hypotension.
Vision changes.
Irregular heartbeat.
Chest pain.
Severe back or muscle pain.
Hearing loss.
Prolonged, painful erection (priapism).
In the event of a suspected overdose, promptly seek emergency medical attention.
TOXICITY
Vardenafil toxicity is primarily associated with overdose, drug interactions, and long-term use, causing an increase in serious side effects related to low blood pressure and cardiac function.
