LIBIDOX

Vardenafil hydrochloride tablets (vardenafil hydrochloride) are administered orally 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).

HCl is designated chemically as piperazine, 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1 - f ]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.

Vardenafil hydrochloride tablets are formulated as orange, round, tablets embossed with "2.5", "5", "10" or "20" on one 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, aspartame, titanium dioxide, ferric oxide red, and ferric oxide yellow.

Vardenafil hydrochloride tablets are indicated for the treatment of erectile dysfunction.

Vardenafil hydrochloride tablets are a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction.

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). 12.2 Pharmacodynamics Effects on Blood Pressure In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute.

The maximum decrease in blood pressure occurred between and 4 hours after dosing.

Following multiple dosing for 31 days, similar blood pressure responses were observed on Day as on Day 1.

Vardenafil may add to the blood pressure lowering effects of antihypertensive agents.

Effects on Blood Pressure and Heart Rate when Vardenafil Hydrochloride Tablets are Combined with Nitrates A study was conducted in which the blood pressure and heart rate response to 0.4 mg nitroglycerin (NTG) sublingually was evaluated in 18 healthy subjects following pretreatment with vardenafil hydrochloride tablets 20 mg at various times before NTG administration.

Vardenafil hydrochloride tablets 20 mg caused an additional time-related reduction in blood pressure and increase in heart rate in association with NTG administration.

The blood pressure effects were observed when vardenafil hydrochloride tablets 20 mg were dosed 1 or 4 hours before NTG and the heart rate effects were observed when 20 mg was dosed 1, 4, or 8 hours before NTG.

Additional blood pressure and heart rate changes were not detected when vardenafil hydrochloride tablets 20 mg were dosed 24 hours before NTG.

Figure 1: Placebo-subtracted point estimates (with 90% CI) of mean maximal blood pressure and heart rate effects of pre-dosing with vardenafil 20 mg at 24, 8, 4, and 1 hour before 0.4 mg NTG sublingually Because the disease state of patients requiring nitrate therapy is anticipated to increase the likelihood of hypotension, the use of vardenafil by patients on nitrate therapy or on nitric oxide donors is contraindicated.

Blood Pressure Effects in Patients on Stable Alpha-Blocker Treatment Three clinical pharmacology studies were conducted in patients with benign prostatic hyperplasia (BPH) on stable-dose alpha-blocker treatment, consisting of alfuzosin, tamsulosin or terazosin.

Study 1: This study was designed to evaluate the effect of 5 mg vardenafil compared to placebo when administered to BPH patients on chronic alpha-blocker therapy in two separate cohorts: tamsulosin 0.4 mg daily (cohort 1, n=21) and terazosin 5 or 10 mg daily (cohort 2, n=21).

The design was a randomized, double blind, cross-over study with four treatments: vardenafil 5 mg or placebo administered simultaneously with the alpha-blocker and vardenafil 5 mg or placebo administered 6 hours after the alpha-blocker.

Blood pressure and pulse were evaluated over the 6-hour interval after vardenafil dosing.

For blood pressure (BP) results see Table 2.

One patient after simultaneous treatment with 5 mg vardenafil and 10 mg terazosin exhibited symptomatic hypotension with standing blood pressure of 80/60 mmHg occurring one hour after administration and subsequent mild dizziness and moderate lightheadedness lasting for 6 hours.

For vardenafil and placebo, five and two patients, respectively, experienced a decrease in standing systolic blood pressure (SBP) of >30 mmHg following simultaneous administration of terazosin.

Hypotension was not observed when vardenafil 5 mg and terazosin were administered 6 hours apart.

Following simultaneous administration of vardenafil 5 mg and tamsulosin, two patients had a standing SBP of <85 mmHg.

A decrease in standing

SBP of >30 mmHg was observed in two patients on tamsulosin receiving simultaneous vardenafil and in one patient receiving simultaneous placebo treatment.

When tamsulosin and vardenafil 5 mg were separated by 6 hours, two patients had a standing SBP <85 mmHg and one patient had a decrease in SBP of >30 mmHg.

There were no severe adverse events related to hypotension reported during the study.

There were no cases of syncope.

Table 2: Mean (95% C.I). maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 5 mg in BPH patients on stable alpha-blocker therapy (Study 1) Alpha-Blocker Simultaneous dosing of Vardenafil 5 mg and Alpha-Blocker, Placebo-Subtracted Dosing of Vardenafil 5 mg and Alpha-Blocker Separated by 6 Hours, Placebo-Subtracted Terazosin Standing SBP -3 (-6.7, 0.1) -4 (-7.4, -0.5) 5 or 10 mg daily Supine SBP -4 (-6.7, -0.5) -4 (-7.1, -0.7) Tamsulosin Standing SBP -6 (-9.9, -2.1) -4 (-8.3, -0.5) 0.4 mg daily Supine SBP -4 (-7, -0.8) -5 (-7.9, -1.7) Blood pressure effects (standing SBP) in normotensive men on stable dose of tamsulosin 0.4 mg following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours are shown in Figure 2.

Blood pressure effects (standing SBP) in normotensive men on stable dose terazosin (5 or 10 mg) following simultaneous administration of vardenafil 5 mg or placebo, or following administration of vardenafil 5 mg or placebo separated by 6 hours, are shown in Figure 3.

Figure 2: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (Study 1) Figure 3: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 5 mg or placebo with stable dose terazosin (5 or 10 mg) in normotensive BPH patients (Study 1) Study 2: This study was designed to evaluate the effect of 10 mg vardenafil (stage 1) and 20 mg vardenafil (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=23) on stable therapy with tamsulosin 0.4 mg or 0.8 mg daily for at least four weeks.

The design was a randomized, double blind, two-period cross-over study.

Vardenafil or placebo was given simultaneously with tamsulosin.

Blood pressure and pulse were evaluated over the 6­ hour interval after vardenafil dosing.

For BP results see

Table 3.

One patient experienced a decrease from baseline in standing SBP of >30 mmHg following vardenafil 10 mg. There were no other instances of outlier blood pressure values (standing SBP <85 mmHg or decrease from baseline in standing SBP of >30 mmHg).

Three patients reported dizziness following vardenafil 20 mg. There were no cases of syncope.

Table 3: Mean (95% C.I). maximal change from baseline in systolic blood pressure (mmHg) following vardenafil and 20 mg in BPH patients on stable alpha-blocker therapy with tamsulosin 0.4 or 0.8 mg daily (Study 2) Vardenafil 10 mg Placebo-subtracted Vardenafil 20 mg Placebo-subtracted Standing SBP -4 (-6.8, -0.3) -4 (-6.8, -1.4) Supine SBP -5 (-8.2, -0.8) -4 (-6.3, -1.8) Blood pressure effects (standing SBP) in normotensive men on stable dose of tamsulosin 0.4 mg following simultaneous administration of vardenafil 10 mg, vardenafil 20 mg or placebo are shown in Figure 4.

Figure 4: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous administration of vardenafil 10 mg (Stage 1), vardenafil 20 mg (Stage 2), or placebo with stable dose tamsulosin 0.4 mg in normotensive BPH patients (Study 2) Study 3: This study was designed to evaluate the effect of single doses of 5 mg vardenafil (stage 1) and 10 mg vardenafil (stage 2) compared to placebo, when administered to a single cohort of BPH patients (n=24) on stable therapy with alfuzosin 10 mg daily for at least four weeks.

The design was a randomized, double blind, 3­ period cross-over study.

Vardenafil or placebo was administered 4 hours after the administration of alfuzosin.

Blood pressure and pulse were evaluated over a 10-hour interval after dosing of vardenafil or placebo.

Table 4.

Table 4: Mean (95% C.I). maximal change from baseline in systolic blood pressure (mmHg) following vardenafil and 10 mg in BPH patients on stable alpha-blocker therapy with alfuzosin 10 mg daily (Study 3) Vardenafil 5 mg Placebo-subtracted Vardenafil 10 mg Placebo-subtracted Standing SBP -2 (-5.8, 1.2) -5 (-8.8, -1.6) Supine SBP -1 (-4.1, 2.1) -6 (-9.4, -2.8) One patient experienced decreases from baseline in standing systolic blood pressure >30 mm Hg after administration of vardenafil 5 mg tablet and vardenafil 10 mg tablet.

No instances of standing systolic blood pressure <85 mm Hg were observed during this study.

Four patients, one dosed with placebo, two dosed with vardenafil 5 mg tablets and one dosed with vardenafil 10 mg tablets, reported dizziness.

Blood pressure effects (standing SBP) in normotensive men on a stable dose of alfuzosin 10 mg following administration of vardenafil 5 mg, vardenafil 10 mg, or placebo separated by 4 hours, are shown in Figure 5.

Figure 5: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following 4 hr separation administration of vardenafil 5 mg (stage 1), vardenafil 10 mg (stage 2) or placebo with stable dose alfuzosin 10 mg in BPH patients (Study 3) Blood pressure effects in normotensive men after forced titration with alpha-blockers: Two randomized, double blind, placebo-controlled clinical pharmacology studies with healthy normotensive volunteers (age range, 45-74 years) were performed after forced titration of the alpha-blocker terazosin to 10 mg daily over 14 days (n=29), and after initiation of tamsulosin 0.4 mg daily for five days (n=24).

There were no severe adverse events related to hypotension in either study.

Symptoms of hypotension were a cause for withdrawal in 2 subjects receiving terazosin and in 4 subjects receiving tamsulosin.

Instances of outlier blood pressure values (defined as standing SBP <85 mmHg and/or a decrease from baseline of standing SBP >30 mmHg) were observed in 9/24 subjects receiving tamsulosin and 19/29 receiving terazosin.

The incidence of subjects with standing

SBP <85 mmHg given vardenafil and terazosin to achieve simultaneous T max led to early termination of that arm of the study.

In most (7/8) of these subjects, instances of standing SBP <85 mmHg were not associated with symptoms.

Among subjects treated with terazosin, outlier values were observed more frequently when vardenafil and terazosin were given to achieve simultaneous T max than when dosing was administered to separate T max by 6 hours.

The following serious adverse reactions with the use of vardenafil hydrochloride tablets (vardenafil) are discussed elsewhere in the labeling: Cardiovascular Effects Priapism Effects on Eye Sudden Hearing Loss QT Prolongation Most common adverse reactions reported ( ≥ 2% of patients) are headache, flushing, nasal congestion, dyspepsia, sinusitis, flu syndrome, dizziness, increased creatine kinase, nausea, back pain.

To report SUSPECTED ADVERSE

REACTIONS, contact Lannett Company, Inc.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Vardenafil hydrochloride tablets were 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 vardenafil hydrochloride tablets compared to 1.1% for placebo.

When vardenafil hydrochloride tablets were taken as recommended in placebo-controlled clinical trials, the following adverse reactions were reported.

Table 1: Adverse Reactions Reported By ≥2% of Patients Treated with Vardenafil Hydrochloride Tablets and More Frequent on Drug than Placebo in Fixed and Flexible Flexible dose studies started all patients at vardenafil hydrochloride tablets 10 mg and allowed decrease in dose to 5 mg or increase in dose to 20 mg based on side effects and efficacy.

Randomized, Controlled Trials of 5 mg, 10 mg, or 20 mg Vardenafil Adverse Reaction Percentage of Patients Reporting Reactions Placebo N = 1199 Vardenafil Hydrochloride Tablets N = 2203 Headache 4% 15% Flushing 1% 11% Rhinitis 3% 9% Dyspepsia 1% 4% Accidental Injury All the events listed in the above table were deemed to be adverse drug reactions with the exception of accidental injury. 2% 3% Sinusitis 1% 3% Flu Syndrome 2% 3% Dizziness 1% 2% Increased Creatine Kinase 1% 2% Nausea 1% 2% Back pain was reported in 2.0% of patients treated with vardenafil hydrochloride tablets and 1.7% of patients on placebo.

Placebo-controlled trials suggested a dose effect in the incidence of some adverse reactions (headache, flushing, dyspepsia, nausea, and rhinitis) over the 5 mg, 10 mg, and 20 mg doses of vardenafil hydrochloride tablets.

Vardenafil hydrochloride tablets and vardenafil orally disintegrating tablets have been administered to over 17,000 men (mean age 54.5, range 18–89 years; 70% White, 5% Black, 13% Asian, 4% Hispanic and 8% Other) during controlled and uncontrolled clinical trials worldwide.

The number of patients treated for 6 months or longer was 3357, and 1350 patients were treated for at least 1 year.

In the placebo-controlled clinical trials for vardenafil hydrochloride tablets and vardenafil orally disintegrating tablets, the discontinuation rate due to adverse events was 1.9% for vardenafil compared to 0.8% for placebo.

The following section identifies additional, less frequent adverse reactions (<2%) reported during the clinical development of vardenafil hydrochloride tablets and vardenafil orally disintegrating tablets.

Excluded from this list are those adverse reactions 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: allergic edema and angioedema, feeling unwell, allergic reactions, chest pain Auditory: tinnitus, vertigo Cardiovascular: palpitation, tachycardia, angina pectoris, myocardial infarction, ventricular tachyarrhythmias, hypotension Digestive: nausea, gastrointestinal and abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increase in transaminases Musculoskeletal: increase in creatine phosphokinase (CPK), increased muscle tone and cramping, myalgia Nervous: paresthesia and dysesthesia, somnolence, sleep disorder, syncope, amnesia, seizure Respiratory: dyspnea, sinus congestion Skin and appendages: erythema, rash Ophthalmologic: visual disturbance, ocular hyperemia, visual color distortions, eye pain and eye discomfort, photophobia, increase in intraocular pressure, conjunctivitis Urogenital: increase in erection, priapism 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of vardenafil hydrochloride tablets.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil.

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.

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 postmarketing experience.

It is not possible to determine whether these events are related directly to the use of vardenafil.

Seizure, seizure recurrence and transient global amnesia have been reported postmarketing in temporal association with vardenafil.

Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil.

In some cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events.

In many cases, medical follow-up information was limited.

It is not possible to determine whether these reported events are related directly to the use of vardenafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors.

The maximum dose of vardenafil hydrochloride tablets for which human data are available is a single 120 mg dose administered to healthy male volunteers.

The majority of these subjects experienced reversible back pain/myalgia and/or "abnormal vision." Single doses up to 80 mg vardenafil and multiple doses up to 40 mg vardenafil administered once daily over 4 weeks were tolerated without producing serious adverse side effects.

When 40 mg of vardenafil was administered twice daily, cases of severe back pain were observed.

No muscle or neurological toxicity was identified.

In cases of overdose, standard supportive measures should be taken as required.

Renal dialysis is not expected to accelerate clearance as vardenafil is highly bound to plasma proteins and not significantly eliminated in the urine.

Administration with nitrates and nitric oxide donors Administration with guanylate cyclase (GC) stimulators, such as riociguat 4.1 Nitrates Administration of vardenafil hydrochloride tablets with nitrates (either regularly and/or intermittently) and nitric oxide donors is contraindicated.

Consistent with the effects of

PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors, including vardenafil hydrochloride tablets, may potentiate the hypotensive effects of nitrates.

A suitable time interval following dosing of vardenafil hydrochloride tablets for the safe administration of nitrates or nitric oxide donors has not been determined. 4.2 Guanylate Cyclase (GC) Stimulators Do not use vardenafil hydrochloride tablets in patients who are using a GC stimulator, such as riociguat.

PDE5 inhibitors, including vardenafil hydrochloride tablets may potentiate the hypotensive effects of GC stimulators.

Vardenafil hydrochloride tablets are taken as needed: For most patients, the starting dose is 10 mg, up to once daily.

Increase to 20 mg or decrease to 5 mg based on efficacy/tolerability.

A starting dose of 5 mg vardenafil hydrochloride tablets should be considered in patients ≥ 65 years of age.

Vardenafil hydrochloride tablets are taken orally, approximately 60 minutes before sexual activity.

The maximum recommended dosing frequency is one tablet per day. Vardenafil hydrochloride tablets may be taken with or without food.

If taking strong or moderate inhibitors of CYP3A4, the dose of vardenafil hydrochloride tablets should be adjusted as follows: Ritonavir: No more than 2.5 mg in a 72-hour period Cobicistat: No more than 2.5 mg in a 72-hour period Indinavir, saquinavir, atazanavir, ketoconazole 400 mg daily, itraconazole 400 mg daily, clarithromycin: No more than 2.5 mg in a 24-hour period Ketoconazole 200 mg daily, itraconazole 200 mg daily, erythromycin: No more than 5 mg in a 24-hour period.

In patients on stable alpha-blocker therapy the recommended starting dose of vardenafil hydrochloride tablets is 5 mg The recommended starting dose of vardenafil hydrochloride tablets is 5 mg in patients with moderate hepatic impairment (Child-Pugh B).

The maximum dose in patients with moderate hepatic impairment should not exceed 10 mg. 2.1 General Dose Information For most patients, the recommended starting dose of vardenafil hydrochloride tablets is 10 mg, taken orally, as needed, 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. Sexual stimulation is required for a response to treatment. 2.2 Use with Food Vardenafil hydrochloride tablets can be taken with or without food. 2.3 Use in Specific Populations Geriatrics: A starting dose of 5 mg vardenafil hydrochloride tablets should be considered in patients ≥65 years of age.

For patients with moderate hepatic impairment (Child-Pugh B), a starting dose of 5 mg vardenafil hydrochloride tablets is recommended.

The maximum dose in patients with moderate hepatic impairment should not exceed 10 mg. Do not use vardenafil hydrochloride tablets in patients with severe hepatic impairment (Child-Pugh C) .

Do not use vardenafil hydrochloride tablets in patients on renal dialysis. 2.4 Concomitant Medications Nitrates: Concomitant use with nitrates and nitric oxide donors in any form is contraindicated Guanylate Cyclase (GC) Stimulators, such as riociguat: Concomitant use is contraindicated.

CYP3A4 Inhibitors: The dosage of vardenafil hydrochloride tablets may require adjustment in patients receiving potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, atazanavir, cobicistat, and clarithromycin as well as in other patients receiving moderate CYP3A4 inhibitors such as erythromycin.

If taking strong or moderate inhibitors of CYP3A4, the dose of vardenafil hydrochloride tablets should be adjusted as follows: Ritonavir: No more than 2.5 mg in a 72-hour period.

Indinavir, saquinavir, atazanavir, ketoconazole 400 mg daily, itraconazole 400 mg daily, clarithromycin: No more than 2.5 mg in a 24-hour period.

Ketoconazole 200 mg daily, itraconazole 200 mg daily, erythromycin: No more than 5 mg in a 24-hour period.

No more than 2.5 mg in a 72 hour period.

In those patients who are stable on alpha-blocker therapy, phosphodiesterase type 5 (PDE5) inhibitors should be initiated at the lowest recommended starting dose.

Concomitant treatment should be initiated only if the patient is stable on his alpha-blocker therapy.

Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure in patients taking a phosphodiesterase (PDE5) inhibitor including vardenafil.

In those patients who are stable on alpha-blocker therapy, vardenafil hydrochloride tablets should be initiated at a dose of 5 mg (2.5 mg when used concomitantly with certain CYP3A4 inhibitors).

A time interval between dosing should be considered when vardenafil hydrochloride tablets are prescribed concomitantly with alpha-blocker therapy.

Vardenafil hydrochloride tablets are formulated as orange, round, tablets embossed with "20" on one side equivalent to 20 mg of vardenafil.

NDC 72162-2236-3: 30 Tablets in a BOTTLE Store at 25°C (77°F); excursions permitted within15-30°C (59-86°F) .

Repackaged/Relabeled by: Bryant Ranch Prepack, Inc.

Burbank, CA 91504.

Vardenafil hydrochloride tablets are not indicated for use in females.

There are no data with the use of vardenafil hydrochloride tablets in pregnant women to inform any drug-associated risks.

In animal reproduction studies conducted in pregnant rats and rabbits, no adverse developmental outcomes were observed with oral administration of vardenafil during organogenesis at exposures for unbound vardenafil and its major metabolite at approximately and 29 times, respectively, the maximum recommended human dose (MRHD) of 20 mg based on AUC.

No evidence of specific potential for teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits that received vardenafil at up to 18 mg/kg/day during organogenesis.

This dose is approximately 100 fold (rat) and 29 fold (rabbit) greater than the AUC values for unbound vardenafil and its major metabolite in humans given the MRHD of 20 mg. In the rat pre-and postnatal development study, the NOAEL (no observed adverse effect level) for maternal toxicity was 8 mg/kg/day. Retarded physical development of pups in the absence of maternal effects was observed following maternal exposure to and 8 mg/kg possibly due to vasodilatation and/or secretion of the drug into milk.

The number of living pups born to rats exposed pre.

• and postnatally was reduced at 60 mg/kg/day. Based on the results of the pre.

• and postnatal study, the developmental NOAEL is less than 1 mg/kg/day. Based on plasma exposures in the rat developmental toxicity study, 1 mg/kg/day in the pregnant rat is estimated to produce total AUC values for unbound vardenafil and its major metabolite comparable to the human AUC at the MRHD of 20 mg.

Vardenafil hydrochloride tablets are not indicated for use in pediatric patients.

Safety and efficacy have not been established in this population.

Elderly males 65 years of age and older have higher vardenafil plasma concentrations than younger males (18 – 45 years), mean C max and AUC were 34% and 52% higher, respectively.

Phase 3 clinical trials included more than 834 elderly patients, and no differences in safety or effectiveness of vardenafil hydrochloride tablets 5, 10, or 20 mg were noted when these elderly patients were compared to younger patients.

However, due to increased vardenafil concentrations in the elderly, a starting dose of 5 mg vardenafil hydrochloride tablets should be considered in patients ≥65 years of age.