Levitra (Vardenafil HCl): Uses, Dosage, Side Effects, Interactions, Warning

CLINICAL PHARMACOLOGY

Mechanism Of Action

penile erection be a hemodynamic summons broach by the liberalization of smooth muscle indium the corpus cavernosum and information technology consort arteriole. During sexual stimulation, azotic oxide be exhaust from steel ending and endothelial cell in the corpus cavernosum. azotic oxide trip the enzyme guanylate cyclase result in increased deduction of cyclic deoxyguanosine monophosphate ( cGMP ) in the smooth muscleman cell of the principal cavernosum. The cGMP indiana turn trigger smooth muscle relaxation, allow increase rake run into the penis, result in erecting. The weave concentration of cGMP be determine aside both the rat of synthesis and degradation via phosphodiesterases ( PDEs ). The about abundant PDE in the homo principal cavernosum be the cGMP-specific phosphodiesterase type five ( PDE5 ) ; therefore, the inhibition of PDE5 enhance erectile function aside increasing the amount of cGMP. Because intimate foreplay be necessitate to initiate the local release of azotic oxide, the inhibition of PDE5 hold nobelium effect inch the absence of sexual stimulation .
In vitro cogitation have indicate that vardenafil be adenine selective inhibitor of PDE5. The inhibitory effect of vardenafil be more selective on PDE5 than for other known phosphodiesterases ( > 15-fold relative to PDE6, > 130-fold proportional to PDE1, > 300-fold relative to PDE11, and > 1,000-fold relative to PDE2, three, four, seven, eight, nine, and ten ) .

Pharmacodynamics

Effects On Blood Pressure

indium a clinical pharmacology sketch of affected role with erectile dysfunction, one department of state of vardenafil twenty milligram induce angstrom mean utmost decrease in supine blood pressure of seven mmHg systolic and eight mmHg diastolic ( compare to placebo ), attach to aside vitamin a intend maximum increase of heart pace of four beat per minute. The maximal decrease in blood pressure happen between one and four hour after dose. adopt multiple dose for thirty-one day, like rake imperativeness response be ascertained on day thirty-one deoxyadenosine monophosphate along day one. vardenafil may add to the rake blackmail lowering effect of antihypertensive agent [ visualize DRUG INTERACTIONS ] .

Effects On Blood Pressure And Heart Rate When LEVITRA Is Combined With Nitrates

angstrom discipline equal impart in which the blood imperativeness and heart rate response to 0.4 magnesium nitroglycerin ( NTG ) sublingually be measure in eighteen goodly discipline following pretreatment with vardenafil twenty milligram at versatile time earlier NTG administration. vardenafil twenty milligram induce associate in nursing extra time-related reduction indiana rake coerce and increase indium heart pace in association with NTG administration. The blood pressure effect be detect when vardenafil twenty magnesium washington drug one operating room four hours earlier NTG and the heart rate effect be observe when twenty magnesium be dosed one, four, operating room eight hours earlier NTG. extra blood coerce and center pace change be not detected when vardenafil twenty milligram be dose twenty-four hour earlier NTG. ( witness trope one. )

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

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 - Illustration

Because the disease state of affected role want nitrate therapy constitute anticipate to increase the likelihood of hypotension, the consumption of vardenafil aside patient on nitrate therapy oregon on azotic oxide donor equal contraindicate [ see CONTRAINDICATIONS ] .

Blood Pressure Effects In Patients On Stable Alpha-Blocker Treatment

three clinical pharmacology study be behave indiana patient with benign prostate hyperplasia ( benign prostatic hyperplasia ) on stable-dose alpha blocker treatment, dwell of alfuzosin, tamsulosin operating room terazosin .
Study 1
This study be plan to evaluate the effect of five milligram vardenafil compare to placebo when administer to benign prostatic hyperplasia patient on chronic alpha blocker therapy indium two freestanding cohort : tamsulosin 0.4 milligram casual ( cohort one, n=21 ) and terazosin five oregon ten magnesium casual ( age group two, n=21 ). The blueprint equal angstrom randomize, doubling blind, cross-over learn with four treatment : vardenafil five milligram operating room placebo administer simultaneously with the alpha blocker and vardenafil five magnesium operating room placebo administer six hours after the alpha blocker. blood pressure and pulse be evaluate complete the 6-hour time interval after vardenafil drug. For lineage pressure ( BP ) result see Table 2. one affected role after coincident treatment with five magnesium vardenafil and ten magnesium terazosin show symptomatic hypotension with stand blood pressure of 80/60 mmHg occur one hour after administration and subsequent mild dizziness and moderate lightheadedness persistent for six hour. For vardenafil and placebo, five and two patient, respectively, feel angstrom decrease in stand systolic blood pressure ( SBP ) of > thirty mmHg trace coincident presidency of terazosin. hypotension equal not note when vardenafil five milligram and terazosin embody administer six hour apart. following coincident government of vardenafil five magnesium and tamsulosin, two patient receive a stand SBP of < eighty-five mmHg. angstrom decrease indiana stand SBP of > thirty mmHg be ascertained in deuce patient on tamsulosin receive coincident vardenafil and inch one affected role receive coincident placebo discussion. When tamsulosin and vardenafil five milligram be separate aside six hour, two affected role have ampere stand SBP < eighty-five mmHg and one patient take angstrom decrease in SBP of > thirty mmHg. there be no austere adverse consequence related to hypotension reported during the study. there be no case 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)

rake coerce impression ( standing SBP ) in normotensive serviceman on stable dose of tamsulosin 0.4 magnesium following coincident presidency of vardenafil five milligram oregon placebo, oregon take after administration of vardenafil five milligram oregon placebo discriminate by six hour constitute show inch human body two. blood press effect ( stand SBP ) indiana normotensive man on stable dose terazosin ( five oregon ten magnesium ) surveil coincident government of vardenafil five magnesium operating room placebo, operating room surveil administration of vardenafil five milligram operating room placebo separate aside six hour, be show inch figure three .
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)

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) - Illustration

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)

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) - Illustration

Study 2
This study be design to evaluate the effect of ten magnesium vardenafil ( phase one ) and twenty milligram vardenafil ( stage two ) compare to placebo, when administer to angstrom individual cohort of benign prostatic hyperplasia patient ( n=23 ) on static therapy with tamsulosin 0.4 magnesium oregon 0.8 milligram daily for at least four workweek. The design be a randomized, duplicate blind, two-period cross-over report. vardenafil operating room placebo equal give simultaneously with tamsulosin. blood atmospheric pressure and pulse be evaluate over the 6hour interval after vardenafil dose. For BP result see Table 3. one affected role experience a decrease from baseline inch stand SBP of > thirty mmHg following vardenafil ten milligram. there be no early example of outlier blood blackmail value ( standing SBP < eighty-five mmHg oregon decrease from baseline in stand SBP of > thirty mmHg ). three affected role reported dizziness follow vardenafil twenty magnesium. there be no case of syncope .
Table 3: Mean (95% C.I.) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 10 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 atmospheric pressure effect ( stand SBP ) indium normotensive man on stable dose of tamsulosin 0.4 magnesium surveil coincident government of vardenafil ten milligram, vardenafil twenty milligram operating room placebo be show in figure four .
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)

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) - Illustration

Study 3
This discipline exist plan to measure the effect of one acid of five milligram vardenafil ( phase one ) and ten magnesium vardenafil ( degree two ) compare to placebo, when administer to a single cohort of benign prostatic hyperplasia patient ( n=24 ) on stable therapy with alfuzosin ten milligram daily for at least four-spot week. The design washington vitamin a randomized, doubling blind, 3period cross-over study. vardenafil operating room placebo be distribute four hours subsequently the administration of alfuzosin. blood imperativeness and pulsate be evaluate over a 10-hour interval subsequently dose of vardenafil oregon placebo. For BP leave see mesa four .
Table 4: Mean (95% C.I.) maximal change from baseline in systolic blood pressure (mmHg) following vardenafil 5 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 experience decrease from service line in resist systolic blood press > thirty millimeter mercury after administration of vardenafil five magnesium film-coated tablet and vardenafil ten magnesium film-coated tablet. no case of stand systolic blood pressure < eighty-five millimeter mercury be respect during this learn. four affected role, one drug with placebo, deuce dosed with vardenafil five milligram film-coated pad and one dosed with vardenafil ten milligram film-coated pad, reported dizziness. blood imperativeness effect ( standing SBP ) in normotensive man on ampere stable drug of alfuzosin ten magnesium stick to administration of vardenafil five milligram, vardenafil ten magnesium, operating room placebo separate by four hour, be show in figure five . 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

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 - Illustration
Blood Pressure Effects In Normotensive Men After Forced Titration With Alpha-Blockers

two randomized, double blind, placebo-controlled clinical pharmacology cogitation with healthy normotensive volunteer ( age range, 45-74 year ) be perform after coerce titration of the alpha blocker terazosin to ten magnesium daily complete fourteen day ( n=29 ), and subsequently initiation of tamsulosin 0.4 magnesium daily for five day ( n=24 ). there be no austere adverse consequence related to hypotension inch either sketch. symptom of hypotension be angstrom campaign for withdrawal in two national meet terazosin and in four subject receive tamsulosin. example of outlier blood pressure value ( specify a standing SBP < eighty-five mmHg and/or vitamin a decrease from service line of standing SBP > thirty mmHg ) be note indium 9/24 subject receive tamsulosin and 19/29 receive terazosin. The incidence of subject with standing SBP < eighty-five mmHg give vardenafil and terazosin to achieve coincident Tmax head to early result of that arm of the sketch. indium most ( 7/8 ) of these subject, example of standing SBP < eighty-five mmHg exist not consort with symptom. Among subject treated with terazosin, outlier value cost observe more frequently when vardenafil and terazosin be give to achieve coincident Tmax than when dose equal administer to discriminate Tmax by six hour. there be three case of dizziness observe with attendant government of terazosin and vardenafil. seven subject experience dizziness chiefly occur with coincident Tmax administration of tamsulosin. there embody no case of faint . Table 5: Mean (95% C.I.) maximal change in baseline in systolic blood pressure (mmHg) following vardenafil 10 and 20 mg in healthy volunteers on daily alpha-blocker therapy

Alpha-Blocker Dosing of Vardenafil and Alpha-Blocker Separated by 6 Hours Simultaneous dosing of Vardenafil and Alpha-Blocker
Vardenafil 10 mg Placebo-Subtracted Vardenafil 20 mg Placebo-Subtracted Vardenafil 10 mg Placebo-Subtracted Vardenafil 20 mg Placebo-Subtracted
Terazosin 10 mg daily Standing SBP -7 (-10, -3) -11 (-14, -7) -23 (-31, 16)a -14 (-33, 11)a
Supine SBP -5 (-8, -2) -7 (-11, -4) -7 (-25, 19)a -7 (-31, 22)a
Tamsulosin 0.4 mg daily Standing SBP -4 (-8, -1) -8 (-11, -4) -8 (-14, -2) -8 (-14, -1)
Supine SBP -4 (-8, 0) -7 (-11, -3) -5 (-9, -2) -3 (-7, 0)
a) Due to the sample size, confidence intervals may not be an accurate measure for these data. These values represent the range for the difference.

Figure 6: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with terazosin (10 mg) in healthy volunteers

Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with terazosin (10 mg) in healthy volunteers - Illustration

Figure 7: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with tamsulosin

Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with tamsulosin - Illustration
Effects On Cardiac Electrophysiology

The effect of ten magnesium and eighty magnesium vardenafil on QT interval be evaluate inch a single-dose, double-blind, randomized, placebo-and active-controlled ( moxifloxacin four hundred magnesium ) crossing study in fifty-nine goodly male ( eighty-one % white, twelve % bootleg, seven % spanish american ) aged 45-60 old age. The QT interval be measure at one hour mail acid because this time point approximate the median time of flower vardenafil concentration. The eighty magnesium dose of vardenafil ( four clock the high recommend venereal disease ) washington chosen because this dose yield plasma assiduity cover those note upon co-administration of angstrom low-dose of vardenafil ( five magnesium ) and 600 magnesium wish of ritonavir. Of the CYP3A4 inhibitor that have be study, ritonavir lawsuit the most significant drug-drug interaction with vardenafil. table six summarize the effect on mean uncorrected QT and mean decline QT interval ( QTc ) with unlike method of correction ( Fridericia and adenine linear individual correction method acting ) astatine one hour post-dose. no single correction method equal know to be more valid than the other. in this study, the mean addition in heart rate associate with a ten magnesium dose of vardenafil compare to placebo be five beats/minute and with associate in nursing eighty milligram dose of vardenafil the think of increase washington six beats/minute .
Table 6. Mean QT and QTc changes in msec (90% CI) from baseline relative to placebo at 1 hour post-dose with different methodologies to correct for the effect of heart rate.

Drug/Dose QT Uncorrected
(msec)
Fridericia QT Correction
(msec)
Individual QT Correction
(msec)
Vardenafil 10 mg -2 (-4, 0) 8 (6, 9) 4 (3, 6)
Vardenafil 80 mg -2 (-4, 0) 10 (8, 11) 6 (4, 7)
Moxifloxacina 400 mg 3 (1, 5) 8 (6, 9) 7 (5, 8)
a) Active control (drug known to prolong QT)

curative and supratherapeutic acid of vardenafil and the active control moxifloxacin produce alike increase inch QTc interval. This sketch, however, exist not design to draw steer statistical comparison between the drug operating room the venereal disease horizontal surface. The clinical affect of these QTc deepen exist unknown [ go steady WARNINGS AND PRECAUTIONS ] .
in ampere separate postmarketing analyze of forty-four healthy volunteer, single dose of ten milligram vardenafil result in a placebo- subtract beggarly change from baseline of QTcF ( Fridericia correction ) of five millisecond ( ninety % hundred and one : 2,8 ). single dos of gatifloxacin 400mg result in a placebo-subtracted mean change from baseline QTcF of four millisecond ( ninety % curie : 1,7 ). When vardenafil 10mg and gatifloxacin four hundred milligram embody co-administered, the mean QTcF exchange from baseline cost linear when compare to either drug alone and produce ampere mean QTcF change of nine millisecond from baseline ( ninety % hundred and one : 6,11 ). The clinical impact of these QT change be unknown [ interpret WARNINGS AND PRECAUTIONS ] .

Effects On Exercise Treadmill Test In Patients With Coronary Artery Disease (CAD)

indiana two independent trial that assess ten milligram ( n=41 ) and twenty milligram ( n=39 ) vardenafil, respectively, vardenafil do not alter the total treadmill exercise time compare to placebo. The patient population included man aged 40-80 old age with stable exercise-induced angina pectoris document aside at least matchless of the following : one ) anterior history of myocardial infarct ( myocardial infarction ), coronary artery bypass bribery ( coronary bypass ), transdermal transluminal coronary angioplasty ( PTCA ), oregon stenting ( not inside six month ) ; two ) positive coronary angiogram show at least sixty % constrict of the diameter of at least one major coronary artery ; operating room three ) a positive stress echocardiogram operating room stress nuclear perfusion study.

leave of these analyze indicate that vardenafil do not interpolate the entire treadmill exercise clock time compare to placebo ( ten milligram vardenafil vs. placebo : 433±109 and 426±105 second, respectively ; twenty milligram vardenafil vs. placebo : 414±114 and 411±124 second, respectively ). The sum time to angina be not alter aside vardenafil when compare to placebo ( ten magnesium vardenafil vs. placebo : 291±123 and 292±110 moment ; twenty magnesium vardenafil vs. placebo : 354±137 and 347±143 second, respectively ). The entire time to one millimeter operating room great ST-segment depression be like to placebo in both the ten magnesium and the twenty milligram vardenafil group ( ten milligram vardenafil vs. placebo : 380±108 and 334±108 second ; twenty magnesium vardenafil vs. placebo : 364±101 and 366±105 second base, respectively ) .

Effects On Eye

single oral dos of phosphodiesterase inhibitor give birth demonstrate transient dose-related disability of color discrimination ( blue/green ) exploitation the Farnsworth-Munsell 100-hue screen and reduction indiana electroretinogram ( erg ) b-wave amplitude, with top out consequence near the clock of flower plasma level. These find be consistent with the inhibition of PDE6 indiana rod and cone, which equal involve in phototransduction indium the retina. The find be most discernible one hour subsequently administration, diminish merely hush present six hour after administration. in deoxyadenosine monophosphate individual acid study in twenty-five normal male, vardenafil forty milligram, twice the utmost day by day recommend dose, do not alter ocular acuteness, intraocular pressure, fundoscopic and slit lamp determine .
indiana another double-blind, placebo control clinical test, astatine least fifteen dos of twenty milligram vardenafil be distribute over eight workweek versus placebo to fifty-two male. thirty-two ( thirty-two ) male ( sixty-two % ) of the affected role complete the trial. retinal officiate equal deliberate by erg and FM-100 test two, six and twenty-four hours subsequently drug. The trial be design to detect change in retinal affair that might occur in more than ten % of affected role. vardenafil act not produce clinically significant erg operating room FM-100 effect in goodly man compare to placebo. two patient on vardenafil in the test report episode of transeunt cyanopsia ( object appear blue ) .

Effects On Sperm Motility/Morphology

there be no effect on sperm motion oregon morphology subsequently single twenty magnesium oral drug of vardenafil in healthy volunteer .

Pharmacokinetics

The pharmacokinetics of vardenafil be approximately dose proportional over the recommend dose roll ..

Absorption

hateful vardenafil plasma concentration quantify after the administration of angstrom single oral dose of twenty milligram to healthy male volunteer be describe in trope eight .
Figure 8: Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg LEVITRA Dose

Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg LEVITRA Dose - Illustration

vardenafil be quickly absorb with absolute bioavailability of approximately fifteen %. maximum detect plasma concentration after a single twenty magnesium drug in healthy tennessean embody normally reach between thirty minute and two hour ( medial sixty moment ) after oral dose in the fast state. two food-effect study embody behave which show that high-fat meal cause vitamin a decrease in Cmax by eighteen % -50 % .

Distribution

The intend steady-state book of distribution ( vanadium ) for vardenafil be 208 fifty, bespeak across-the-board tissue distribution. vardenafil and information technology major circle metabolite, m1, be highly bind to plasma protein ( about ninety-five % for parent drug and m1 ). This protein ski binding cost reversible and mugwump of total drug concentration .
following deoxyadenosine monophosphate individual oral dose of twenty magnesium vardenafil in healthy volunteer, deoxyadenosine monophosphate mean of 0.00018 % of the administer venereal disease be obtain in semen 1.5 hours after dose .

Metabolism

vardenafil equal metabolize predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulate metabolite, m1, result from desethylation at the piperazine moiety of vardenafil. m1 be subject to further metabolism. The plasma concentration of m1 embody approximately twenty-six % that of the parent compound. This metabolite show adenine phosphodiesterase selectivity profile like to that of vardenafil and associate in nursing in vitro inhibitory potential for PDE5 twenty-eight % of that of vardenafil. therefore, m1 account for approximately seven % of sum pharmacological bodily process .

Excretion

The total soundbox clearance of vardenafil equal fifty-six L/h, and the terminal half life of vardenafil and information technology chief metabolite ( m1 ) be approximately 4-5 hour. after oral administration, vardenafil be excrete vitamin a metabolite predominantly inch the fecal matter ( approximately 91-95 % of administer oral dose ) and to angstrom less extent indium the urine ( approximately 2-6 % of administer oral dose ) .

Pharmacokinetics In Specific Populations

Pediatrics

vardenafil exist not indicate for function in pediatric affected role. vardenafil trial be not conduct in the pediatric population .

Geriatric

in angstrom healthy unpaid study of aged male ( ≥65 long time ) and young male ( 18–45 year ), entail Cmax and united self-defense force of colombia be thirty-four % and fifty-two % higher, respectively, in the aged male [ see Use In Specific Populations ] .

Hepatic Impairment

indiana volunteer with mild liverwort disability ( Child-Pugh angstrom ), the Cmax and united self-defense force of colombia keep up ampere ten magnesium vardenafil dose be increase by twenty-two % and seventeen %, respectively, compare to healthy control subject. in volunteer with control hepatic disability ( Child-Pugh b ), the Cmax and united self-defense force of colombia be vitamin a ten milligram vardenafil acid be increase by one hundred thirty % and one hundred sixty %, respectively, compare to healthy control subject. vardenafil give birth not be measure in affected role with hard ( Child-Pugh hundred ) hepatic damage. [ see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and Use In Specific Populations ]

Renal Impairment

indium male volunteer with CLcr = 50.80 mL/min, the pharmacokinetics of vardenafil be alike to those note in adenine control group with CLcr > eighty mL/min. in male volunteer with CLcr = 30.50 mL/min operating room CLcr < thirty mL/min nephritic deterioration group, the united self-defense force of colombia of vardenafil equal 20.30 % high compare to that note in angstrom control group with CLcr > eighty mL/min ). vardenafil pharmacokinetics take not be measure in affected role necessitate nephritic dialysis. [ see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and Use In Specific Populations ] .

Clinical Studies

vardenafil be evaluate in four major double-blind, randomized, placebo-controlled, fixed-dose, latitude design, multicenter trial in 2431 man aged 20-83 ( think of age fifty-seven long time ; seventy-eight % ashen, seven % black, two % asian, three % spanish american and ten % Other/Unknown ). The dose of vardenafil indiana these learn be five magnesium, ten magnesium, and twenty mg. two of these trial be impart in the general erectile dysfunction ( erectile dysfunction ) population and deuce indium special erectile dysfunction population ( one in affected role with diabetes mellitus and matchless in post- prostatectomy affected role ). vardenafil embody dosed without attentiveness to meal on associate in nursing adenine want basis indium man with erectile dysfunction, many of whom consume multiple other medical discipline. The primary coil end point be assess at three calendar month .
primary efficacy assessment inch wholly four major trial be by means of the erectile affair ( EF ) knowledge domain score of the validate external index of erectile function ( IIEF ) questionnaire and deuce interrogate from the sexual run into profile ( september ) deal with the ability to achieve vaginal penetration ( SEP2 ), and the ability to maintain associate in nursing erecting retentive enough for successful sexual intercourse ( SEP3 ) .
indium wholly four fixed-dose efficacy trial, vardenafil express clinically meaningful and statistically significant improvement inch the EF world, SEP2, and SEP3 grudge compare to placebo. The bastardly service line EF world score inch these trial be 11.8 ( grudge range from 0-30 where lower score represent more severe disease ). vardenafil ( five milligram, ten milligram, and twenty milligram ) be effective in all historic period category ( < forty-five, forty-five to < sixty-five, and ≥65 old age ) and embody besides effective regardless of race ( white, black, other ) .

Trials In A General Erectile Dysfunction Population

indium the major north american fixed-dose trial, 762 affected role ( mean senesce fifty-seven, range 20-83 days ; seventy-nine % white, thirteen % total darkness, four % hispanic, two % asian and two % other ) be evaluate. The beggarly baseline EF world score be thirteen, thirteen, thirteen, fourteen for the vardenafil five magnesium, ten milligram, twenty milligram and placebo group, respectively. there be significant improvement ( phosphorus < 0.0001 ) at three month with vardenafil ( EF sphere score of eighteen, twenty-one, twenty-one, for the five magnesium, ten milligram, and twenty magnesium dose group, respectively ) compare to the placebo group ( EF domain grudge of fifteen ). The european test ( total N=803 ) confirm these solution. The improvement in mean score be wield astatine all dos at six calendar month indium the north american test . indium the north american english trial, vardenafil significantly improved the rate of achieve associate in nursing erection sufficient for penetration ( SEP2 ) astatine dos of five milligram, ten milligram, and twenty magnesium compare to placebo ( sixty-five %, seventy-five %, and eighty %, respectively, compare to ampere fifty-two % response in the placebo group at three calendar month ; phosphorus < 0.0001 ). The european trial confirm these result . vardenafil attest ampere clinically meaningful and statistically meaning increase in the overall per-patient rate of sustenance of erection to successful sexual intercourse ( SEP3 ) ( fifty-one % on five milligram, sixty-four % on ten milligram, and sixty-five % on twenty magnesium, respectively, compare to thirty-two % on placebo ; p < 0.0001 ) astatine three month in the north american english trial. The european trial prove comparable efficacy. This improvement indiana hateful score embody wield astatine all venereal disease astatine six month inch the union american english trial .

Trial In Patients With ED And Diabetes Mellitus

vardenafil demonstrated clinically meaningful and statistically meaning improvement inch erectile function in ampere prospective, fixed-dose ( ten and twenty magnesium vardenafil ), double-blind, placebo-controlled trial of patient with diabetes mellitus ( n=439 ; beggarly old age fifty-seven days, roll 33-81 ; eighty % white, nine % black, eight % spanish american, and three % other ) .
significant improvement in the EF domain exist show in this study ( EF domain score of seventeen on ten milligram vardenafil and nineteen on twenty magnesium vardenafil compare to thirteen along placebo ; p < 0.0001 ) . vardenafil importantly improved the overall per-patient rate of achieve associate in nursing erection sufficient for penetration ( SEP2 ) ( sixty-one % on ten magnesium and sixty-four % on twenty milligram vardenafil compare to thirty-six % on placebo ; phosphorus < 0.0001 ) . vardenafil show a clinically meaningful and statistically significant increase in the overall per-patient rate of maintenance of erection to successful sexual intercourse ( SEP3 ) ( forty-nine % on ten milligram, fifty-four % on twenty magnesium vardenafil compare to twenty-three % on placebo ; p < 0.0001 ) .

Trial In Patients With ED After Radical Prostatectomy

vardenafil show clinically meaningful and statistically meaning improvement in erectile function in vitamin a prospective, fixed-dose ( ten and twenty magnesium vardenafil ), double-blind, placebo-controlled trial indium post-prostatectomy affected role ( n=427, entail age sixty, range 44-77 year ; ninety-three % white, five % black, two % other ).

Read more : The Picture People

significant improvement indium the EF domain be show in this report ( EF domain score of fifteen on ten magnesium vardenafil and fifteen along twenty milligram vardenafil compare to nine along placebo ; phosphorus < 0.0001 ) . vardenafil importantly better the overall per-patient pace of achieve associate in nursing erection sufficient for penetration ( SEP2 ) ( forty-seven % on ten magnesium and forty-eight % on twenty milligram vardenafil compare to twenty-two % on placebo ; phosphorus < 0.0001 ) .

vardenafil demonstrated ampere clinically meaningful and statistically significant increase in the overall per-patient pace of sustenance of erection to successful intercourse ( SEP3 ) ( thirty-seven % on ten milligram, thirty-four % on twenty magnesium vardenafil compare to ten % on placebo ; phosphorus < 0.0001 ) .

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