Levitra Information
Levitra (Vardenafil hydrochloride) Description
Levitra (Vardenafil hydrochloride) 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-propylimidazo[5,1-][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-4-ethyl-, monohydrochloride 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 (Vardenafil hydrochloride) is formulated as orange, round, film-coated 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.
Levitra (Vardenafil hydrochloride) Clinical Pharmacology
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
Levitra (Vardenafil hydrochloride) Clinical Studies
Levitra (Vardenafil hydrochloride) was evaluated in four major double-blind, randomized, placebo-controlled, fixed-dose, parallel design, multicenter trials in 2431 men aged 20-83 (mean age 57 years; 78% White, 7% Black, 2% Asian, 3% Hispanic and 10% Other/Unknown). The doses of Levitra (Vardenafil hydrochloride) in these studies were 5 mg, 10 mg, and 20 mg. Two of these trials were conducted in the general ED population and two in special ED populations (one in patients with diabetes mellitus and one in post-prostatectomy patients). Levitra (Vardenafil hydrochloride) was dosed without regard to meals on an as needed basis in men with erectile dysfunction (ED), many of whom had multiple other medical conditions. The primary endpoints were assessed at 3 months.
Primary efficacy assessment in all four major trials was by means of the Erectile Function (EF) Domain score of the validated International Index of Erectile Function (IIEF) Questionnaire and two questions from the Sexual Encounter Profile (SEP) dealing with the ability to achieve vaginal penetration (SEP2), and the ability to maintain an erection long enough for successful intercourse (SEP3).
In all four fixed-dose efficacy trials, Levitra (Vardenafil hydrochloride) showed clinically meaningful and statistically significant improvement in the EF Domain, SEP2, and SEP3 scores compared to placebo. The mean baseline EF Domain score in these trials was 11.8 (scores range from 0-30 where lower scores represent more severe disease). Levitra (Vardenafil hydrochloride) (5 mg, 10 mg, and 20 mg) was effective in all age categories (<45, 45 to <65, and ≥65 years) and was also effective regardless of race (White, Black, Other).
In the North American trial, Levitra (Vardenafil hydrochloride) significantly improved the rates of achieving an erection sufficient for penetration (SEP2) at doses of 5 mg, 10 mg, and 20 mg compared to placebo (65%, 75%, and 80%, respectively, compared to a 52% response in the placebo group at 3 months; p <0.0001). The European trial confirmed these results.
Levitra (Vardenafil hydrochloride) demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (51% on 5 mg, 64% on 10 mg, and 65% on 20 mg, respectively, compared to 32% on placebo; p <0.0001) at 3 months in the North American trial. The European trial showed comparable efficacy. This improvement in mean score was maintained at all doses at 6 months in the North American trial.
Significant improvements in the EF Domain were shown in this study (EF Domain scores of 17 on 10 mg Levitra (Vardenafil hydrochloride) and 19 on 20 mg Levitra (Vardenafil hydrochloride) compared to 13 on placebo; p <0.0001).
Levitra (Vardenafil hydrochloride) significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (61% on 10 mg and 64% on 20 mg Levitra (Vardenafil hydrochloride) compared to 36% on placebo; p <0.0001).
Levitra (Vardenafil hydrochloride) demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (49% on 10 mg, 54% on 20 mg Levitra (Vardenafil hydrochloride) compared to 23% on placebo; p <0.0001).
Significant improvements in the EF Domain were shown in this study (EF Domain scores of 15 on 10 mg Levitra (Vardenafil hydrochloride) and 15 on 20 mg Levitra (Vardenafil hydrochloride) compared to 9 on placebo; p <0.0001).
Levitra (Vardenafil hydrochloride) significantly improved the overall per-patient rate of achieving an erection sufficient for penetration (SEP2) (47% on 10 mg and 48% on 20 mg Levitra (Vardenafil hydrochloride) compared to 22% on placebo; p <0.0001).
Levitra (Vardenafil hydrochloride) demonstrated a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful intercourse (SEP3) (37% on 10 mg, 34% on 20 mg Levitra (Vardenafil hydrochloride) compared to 10% on placebo; p <0.0001).
Levitra (Vardenafil hydrochloride) Indications And Usage
Levitra (Vardenafil hydrochloride) is indicated for the treatment of erectile dysfunction.
Levitra (Vardenafil hydrochloride) Warnings
General:
Left Ventricular Outflow Obstruction:
Levitra (Vardenafil hydrochloride) Precautions
The evaluation of erectile dysfunction should include a determination of potential underlying causes, a medical assessment, and the identification of appropriate treatment.
Before prescribing Levitra (Vardenafil hydrochloride) , it is important to note the following:
Levitra (Vardenafil hydrochloride) Adverse Reactions
Levitra (Vardenafil hydrochloride) was administered to over 4430 men (mean age 56, range 18-89 years; 81% White, 6% Black, 2% Asian, 2% Hispanic and 9% Other) during controlled and uncontrolled clinical trials worldwide. Over 2200 patients were treated for 6 months or longer, and 880 patients were treated for at least 1 year.
In placebo-controlled clinical trials, the discontinuation rate due to adverse events was 3.4% for Levitra (Vardenafil hydrochloride) compared to 1.1% for placebo.
When Levitra (Vardenafil hydrochloride) was taken as recommended in placebo-controlled clinical trials, the following adverse events were reported (see ).
Back pain was reported in 2.0% of patients treated with Levitra (Vardenafil hydrochloride) and 1.7% of patients on placebo.
Placebo-controlled trials suggested a dose effect in the incidence of some adverse events (headache, flushing, dyspepsia, nausea, rhinitis) over the 5 mg, 10 mg, and 20 mg doses of Levitra (Vardenafil hydrochloride) . The following section identifies additional, less frequent events (<2%) reported during the clinical development of Levitra (Vardenafil hydrochloride) . Excluded from this list are those events that are infrequent and minor, those events that may be commonly observed in the absence of drug therapy, and those events that are not reasonably associated with the drug.
BODY AS A WHOLE: anaphylactic reaction (including laryngeal edema), asthenia, face edema, pain
AUDITORY: sudden decrease or loss of hearing, tinnitus
CARDIOVASCULAR: angina pectoris, chest pain, hypertension, hypotension, myocardial ischemia, myocardial infarction, palpitation, postural hypotension, syncope, tachycardia
DIGESTIVE: abdominal pain, abnormal liver function tests, diarrhea, dry mouth, dysphagia, esophagitis, gastritis, gastroesophageal reflux, GGTP increased, vomiting
MUSCULOSKELETAL: arthralgia, back pain, myalgia, neck pain
NERVOUS: hypertonia, hypesthesia, insomnia, paresthesia, somnolence, vertigo
RESPIRATORY: dyspnea, epistaxis, pharyngitis
SKIN AND APPENDAGES: photosensitivity reaction, pruritus, rash, sweating
OPHTHALMOLOGIC: abnormal vision, blurred vision, chromatopsia, changes in color vision, conjunctivitis (increased redness of the eye), dim vision, eye pain, glaucoma, photophobia, watery eyes
UROGENITAL: abnormal ejaculation, priapism (including prolonged or painful erections)
Levitra (Vardenafil hydrochloride) Post-marketing Experience
Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including Levitra (Vardenafil hydrochloride) . Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient’s underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors (see , ).
Visual disturbances including vision loss (temporary or permanent), such as visual field defect, retinal vein occlusion, and reduced visual acuity, have also been reported rarely in post-marketing experience. It is not possible to determine whether these events are related directly to the use of Levitra (Vardenafil hydrochloride) .
Levitra (Vardenafil hydrochloride) Overdosage
The maximum dose of Levitra (Vardenafil hydrochloride) for which human data are available is a single 120 mg dose administered to eight healthy male volunteers. The majority of these subjects experienced reversible back pain/myalgia and/or “abnormal vision.”
In cases of overdose, standard supportive measures should be taken as required. Renal dialysis is not expected to accelerate clearance because vardenafil is highly bound to plasma proteins and is not significantly eliminated in the urine.
Levitra (Vardenafil hydrochloride) Dosage And Administration
For most patients, the recommended starting dose of Levitra (Vardenafil hydrochloride) is 10 mg, taken orally approximately 60 minutes before sexual activity. The dose may be increased to a maximum recommended dose of 20 mg or decreased to 5 mg based on efficacy and side effects. The maximum recommended dosing frequency is once per day. Levitra (Vardenafil hydrochloride) can be taken with or without food. Sexual stimulation is required for a response to treatment.
Levitra (Vardenafil hydrochloride) How Supplied
Levitra (Vardenafil hydrochloride) (vardenafil HCl) is formulated as orange, film-coated round tablets with debossed “BAYER” cross on one side and “2.5”, “5”, “10”, and “20” on the other side equivalent to 2.5 mg, 5 mg, 10 mg, and 20 mg of vardenafil, respectively.
Levitra (Vardenafil hydrochloride)
Levitra (Vardenafil hydrochloride)
Levitra (Vardenafil hydrochloride)
