Levitra (Vardenafil): LEVITRA® is an oral therapy for the treatment of erectile dysfunction. This
monohydrochloride salt of vardenafil is a selective inhibitor of cyclic guanosine
monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).
Vardenafil HCl is designated chemically as piperazine, 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7
and has the following structural formula:
Vardenafil HCl is a nearly colorless, solid substance with a molecular weight of 579.1 g/mol
and a solubility of 0.11 mg/mL in water. LEVITRA is formulated as orange, round, filmcoated tablets with “BAYER” cross debossed on one side and “2.5”, “5”, “10”, and “20” on
the other side corresponding to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively.
In addition to the active ingredient, vardenafil HCl, each tablet contains microcrystalline
cellulose, crospovidone, colloidal silicon dioxide, magnesium stearate, hypromellose,
polyethylene glycol, titanium dioxide, yellow ferric oxide, and red ferric oxide.
Mechanism of Action
Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the
corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is
released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide
activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine
monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in
turn triggers smooth muscle relaxation, allowing increased blood flow into the penis,
resulting in erection. The tissue concentration of cGMP is regulated by both the rates of
synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the
human corpus cavernosum is the cGMP-specific phosphodiesterase type 5 (PDE5); therefore,
the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP.
Because sexual stimulation is required to initiate the local release of nitric oxide, the
inhibition of PDE5 has no effect in the absence of sexual stimulation.
In vitro studies have shown that vardenafil is a selective inhibitor of PDE5. The inhibitory
effect of vardenafil is more selective on PDE5 than for other known phosphodiesterases (>15
fold relative to PDE6, >130-fold relative to PDE1, >300-fold relative to PDE11, and >1,000
fold relative to PDE2, 3, 4, 7, 8, 9, and 10).
The pharmacokinetics of vardenafil are approximately dose proportional over the
recommended dose range. Vardenafil is eliminated predominantly by hepatic metabolism,
mainly by CYP3A4 and to a minor extent, CYP2C isoforms. Concomitant use with potent
CYP3A4 inhibitors such as ritonavir, indinavir, ketoconazole, as well as moderate CYP3A
inhibitors such as erythromycin results in significant increases of plasma levels of vardenafil
(see PRECAUTIONS, WARNINGS and DOSAGE AND ADMINISTRATION).