Each tablet contains 11.85 mg of varadenafil hydrochloride eq. to 10 mg vardenafil base. For a full list of excipients, see section 6.1

Treatment of erectile dysfunction in adult men.
Erectile dysfunction the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. In order for Vardarict to be effective, sexual stimulation is required.
Vardarict is not indicated for use by women.

Use in adult men
The recommended dose is 10 mg taken as needed approximately 25 to 60 minutes before sexual activity. Based on efficacy and tolerability the dose may be increased to 20 mg or decreased to 5 mg. The maximum recommended dose is 20 mg. The maximum recommended dosing frequency is once per day .Vardarict can be taken with or without food. The onset of activity may be delayed if taken with a high fat meal (see section 5.2)
Use in elderly men
Dosage adjustments are not required in elderly patients. However, an increase to a maximum 20 mg dose should be carefully considered depending on the individual tolerability (see section 4.4 and 4.8)
Use In children and adolescents
Vardarict is not indicated for individuals below 18 years of age. There is no relevant indication for use of Vardarict in children.
Use in patients with hepatic impairment
A starting dose of 5 mg should be considered in patients with mild and moderate hepatic impairment (Child – Pugh A – B). Based on tolerability and efficacy, the dose may subsequently be increased. The maximum dose recommended in patients with moderate hepatic impairment (Child – Pugh B) is 10 mg. (see section 4.3 and 5.2) Use in patients with renal impairment
No dosage adjustment is required in patients with mild to moderate renal impairment.
In patients with severe renal impairment (creatinine clearance <30 ml / min). A starting dose of 5 mg should be considered. Based on tolerability and efficacy the dose may be increase to 10 mg and 20 mg.
Use in patients using other medicinal products
When used in combination with the CYP 3A4 inhibitors such as erythromycin or clarithromycin, the dose of vardenafil should not exceed 5 mg (see section 4.5) 
For oral use

Hypersensitivity to the active substance or to any of the excipients
The co-administration of vardenafil with nitrates or nitric oxide donors (such as amyl nitrite) in any form is contraindicated (see section 4.5 and 5.1)
Vardarict is contraindicated in patients who have loss of vision in one eye because of non – arteritic anterior ischemic optic neuropathy (NAION).
Regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure (see section 4.4).
Agents for the treatment of erectile dysfunction should generally not be used in men for whom sexual activity is inadvisable (e.g. patients with severe cardiovascular disorders such as unstable angina or severe cardiac failure [New York Heart Association lll or lV]
The safety of vardenafil has not been studied in the following sub-groups of patients and its use is therefore contraindicated until further information is available:
- Severe hepatic impairment (child-pugh c)
- End stage renal disease requiring dialysis
- Hypotension (blood pressure <90/50 mmHg)
- Recent history of stroke or myocardial infarction (within the last 6 months)
- Unstable angina and known hereditary retinal degenerative disorders such as retinitis pigmentosa
Concomitant use of vardenafil with the potent CYP3A4 inhibitors ketoconazole and itraconazole (oral form) is contraindicated in men older than 75 years.
Concomitant use of vardenafi with HIV protease inhibitors such as ritonavir and indinavir is contraindicated, as they are very potent inhibitors of CYP3A4 (see section 4. 5)

A medical history and physical examination should be undertaken to diagnose erectile dysfunction and determine potential underlying causes, before pharmacological treatment is considered.
Prior to initiating any treatment for erectile dysfunction physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk 
associated with sexual activity (see section 4.3). Vardenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1). Patients with left ventricular outflow obstruction, e.g. aortic stenosis and idiopathic hypertrophic subaortic stenosis, can be sensitive to the action of vasodilators including Type 5 phosphodiesterase inhibitors.
Agents for the treatment of erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (such as angulations, cavernosal fibrosis or Peyronie’s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma or leukemia).
The safety and efficacy of combinations of vardenafil with other treatments for erectile dysfunction have not been studied. Therefore the use of such combinations is not recommended.
The concomitant use of alpha-blockers and vardenafil may lead to symptomatic hypotension in some patients because both are vasodilators.
Concomitant treatment with vardenafil should only be initiated if the patient has been stabilized on his alpha-blocker therapy. In those patients who are stable on
alpha-blocker therapy, vardenafil should be initiated at the lowest recommended starting dose of 5 mg. vardenadil may be administered at any time with tamsulosin. with other alpha-blockers at a time separation of dosing should be considered when vardenadil is prescribed concomitantly (see section 4.5). In those patients already taking an optimized dose of vardenafil, alpha-blocker therapy should be intitiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure in patients taking vardenafil.
Concomitant use of vardenfal with potent CYP 3A4 inhibitors such as itraconazole and ketoconazole (oral form) should be avoided as very high plasma concentration of vardenafil are reached if the medicinal products are combined (see section 4.5 and 4.3).
Vardenafi dose adjustment might be necessary if moderate CYP 3A4 inhibitors such as erythromycin and clarthromycin, are given concomitantly (see section 4.5 and 4.2). Concomitant intake of grapefruit juice is expected to increase the plasma concentrations of vardenfil. The combination should be avoided (see section 4.5).
Single oral doses of 10 mg and 80 mg of vardenafil have been shown to prolong the QTc interval by a mean of 8 msec and 10 msec, respectively, and single dose of 10 mg vardenafil co-administered concomitantly with 400 mg gatifloxacin, a drug with comparable QT effect, showed an additive QTc effect of 4 msec when compared to either drug alone.The clinical impact of these QT changes is unknown (see section 5.1).
The clinical relevance of this finding is unknown and cannot be generalized to all patients under all circumstances, as it will depend on the individual risk factors and susceptibilities that may be present at any time in any given patient. Medicinal products that may prolong QTc interval, including vardenafil, are best avoided in patients with relevant risk factors, for example, hypokalaemia; congenital QT prolongation; concomitant administration of antiarrhythmic medicinal products in Class 1 a (e.g. quinidine, procainamide ), or Class lll (e.g. amiodarone,sotalol)
Visual defects and cases of non-arteritic ischemic optic neuropathy (NAION) have been reported in connection with the intake of Vardarict and other PDE5 inhibitors. The patient should be advised that in the case of sudden visual defect, he should stop taking Vardarict and consult immediately a physician (see section 4.3).
Tolerability of the maximum dose of 20 mg may be lower in elderly patients (≥ 65 years old) (see section 4.2 and 4.8).
In vitro studies with human platelets indicate that vardenafil has no anti-aggregatory effect by its own, but at high (super – therapeutic) concentrations varddenafil, 
potentiates the anti-aggregatory effect of the nitric oxide donor sodium nitroprusside. In humans, vardenafil had no effect on bleeding time alone or in combination with acetyl salicylic acid (see section 4.5). There is no safety information available on the administration of vardenafil to patients with bleeding disorders or active peptic ulceration. Therefore vardenafil should be administered to these patients only after careful benefit – risk assessment.

Effects of other medicinal products on vardenafil
In vitro studies:
Vardenafil is metabolized predominantly by hepatic enzymes via cytochrome P450 (CYP) isoform 3A4, with some contribution from CYP3A5 and CYP2C isoform. Therefore, inhibitors of these isoenzymes may reduce vardenafil clearance.
In vivo studies:
Co-administration of the HlV protease inhibitor indinavir (800 mg three times a day), a potent CYP3A4 inhibitor, with vardenafil (10 mg) resulted in a 16 – fold increase in vardenafil AUC and a 7 – fold increase in vardenafil C max. At 24 hours, the plasma levels of vardenafil had fallen to approximately 4% of the maximum vardenafil plasma level (C max).
Co-administration of vardenafil with ritonavir (600 mg twice daily) resulted in a 13-fold increase in vardenafil Cmax and a 49-fold increase in vardenafil AUC 0-24 
when Co-administration with vardenafil 5 mg, the interaction is a consequence of blocking hepatic metabolism of Vardarict by ritonavir, a highly potent CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half – life of Vardarict to 25.7 hours (see section 4.3).
Co-administration of ketoconazole (200 mg), a potent CYP3A4 inhibitor, with vardenafil (5 mg) resulted in a 10 – fold increase in vardenafil AUC and a 4-fold increase in vardenafil C max (see section 4.4).
Although specific interaction studies have not been conducted, concomitant use of vardenafil with potent CYP3A4 inhibitors such as itraconazole and ketoconazole (oral use) 
should be avoided (see section 4.3 and 4.4). In men older than 75 years the concomitant use of vardenafil with itraconazole or ketoconazole is contraindicated (see section 4.3).
Co-administration of erythromycin (500 mg three times a day), a CYP3A4 inhibitor, with vardenafil (5 mg) resulted in a 4 –fold increase in vardenafil AUC and 
3 – fold increase in Cmax. Although a specific interaction study has not been conducted, the Co-administration of clarithromycin can be expected to result in similar effects on vardenafil AUC and Cmax. When used in combination with a moderate CYP3A4 inhibitor such as erythromycin or clarithromycin, vardenafil dose
adjustment might be necessary (see section 4.2 and 4.4). Cimetidine (400 mg twice daily), a non – specific cytochrome P450 inhibitor, had no effects on vardenafil AUC and Cmax when Co-administered with vardenafil (20 mg) to healthy volunteers.
Grapefruit juice being a weak inhibitor of CYP3A4 gut wall metabolism, may give rise to modest increases in plasma levels of vardenafil (see section 4.4).
The pharmacokinetics of vardenafil (20 mg) was not affected by Co-administration with the H2 – antagonist ranitidine (150 mg twice daily), digoxin, Warfarin, 
glibenclamide, alcohol (mean maximum blood alcohol level of 73 mg/dl) or single doses of antacid (magnesium hydroxide/aluminium hydroxide).
Although specific interaction studies were not conducted for all medicinal products, population, pharmacokinetic analysis showed no effect on vardenafil pharmacokinetic of the following concomitant medicinal products: acetylsalicylic acid, ACE – inhibitors, beta – blockers, weak CYP3A4 inhibitors, diuretics and medicinal products for the treatment of diabetes (sulfonylureas and metformin).
Effects of vardenafil on other medicinal products
There are no data on the interaction of vardenafil and non – specific phosphodiesterase inhibitors such as theophylline or dipyridamole.
In vivo studies:
No potentiation of the blood pressure lowering effect of sublingual nitroglycerin (0.4 mg) was observed when vardenafil (10 mg) was given at varying time intervals
(1 h to 24 h) prior to the dose of nitroglycerin in a study in 18 healthy male subjects. Vardenafil 20 mg potentiated the blood pressure lowering effect of sublingual
nitroglycerin (0.4 mg) taken 1 and 4 hours after vardenafil administration to healthy middle aged subjects. No effect on blood pressure was observed when nitroglycerin was taken 24 hours after administration of a single dose of vardenafil 20 mg. However, there is no information on the possible potentiation of the hypotensive effects of nitrates by vardenafil in patients, and concomitant use is therefore contraindicated (see section 4.3).
Nicorandil is a hybrid of potassium channel opener and nitrate. Due to the nitrate component, it has the potential to have serious interaction with vaedenafil.
Since alpha – blocker monotherapy can cause marked lowering of blood pressure, especially postural hypotension and syncope, interaction studies were conducted 
with vardenafil. In tow interaction studies with healthy normotensive volunteers after forced titration of the alpha – blockers tamsulosin or terazosin to high doses, hypotension (in some cases symptomatic) was reported in a significant number of subjects after Co-administration of vardenafil. Among subjects treated with
terazosin, hypotension was observed more frequently when vardenafil and terazosin were given simultaneously than when the dosing was separated by a time interval of 6 hours. 
Based on the results of interaction studies conducted with vardenafil in patients with benign prostatic hyperplasia (BPH) on stable tamsulosin or terazosin therapy:
• When vardenafil was given at doses of 5, 10 or 20 mg on background of stable therapy with tamsulosin, there was no symptomatic reduction in blood pressure, although 3/21 tamsulosin treated subjects exhibited transient standing systolic blood pressures of less than 85 mmHg.
• When vardenafil 5 mg was given simultaneously with terazosin 5 or 10 mg, one of 21 patients experienced symptomatic postural hypotension. Hypotension was not observed when vardenafil 5 mg and terazosin administration was separated by 6 hours.
Therefore, concomitant treatment should be initiated only if the patient is stable on his alpha blocker therapy. In those patients who are stable on alpha – blocker therapy, vardenafil should be initiated at the lowest recommended starting dose of 5 mg. Vardarict may be administrated at any time with tamsulosin. With other alpha blockers a time separation of dosing should be considered when vardenafil is prescribed concomitantly (see section 4.4).
No significant interactions were shown when warfarin (25 mg), which is metabolized by CYP2C9, or digoxin (0.375 mg) was Co-administrated with vardenafil (20 mg). The relative bioavailability of glibenclamide (3.5 mg) was not affected when Co-administrated with vardenafil (20 mg). In a specific study, where vardenafil (20 mg) was co-administrated with slow release nifedipine (30 mg or 60 mg) in hypertensive patients, there was an additional reduction on supine systolic blood pressure of 6 mmHg and supine diastolic blood pressure of 5 mmHg accompanied with an increase in heart rate of 4 bpm.
When vardenafil (20 mg) and alcohol (mean maximum blood alcohol level of 73 mg/d) were taken together, vardenafil did not potentiate the effects of alcohol on blood pressure and heart rate and the pharmacokinetics of vardenafil were not altered.
Vardenafil (10 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid (2 x 81 mg)

Vardaric is not indicated for use in women. There are no studies of vardenafil in pregnant women .

As the dizziness and abnormal vision have been reported in clinical trials with vardenafil, patients should be aware of how they react with vardarict, before driving or operating machinery

Over 9500 patients have received vardenafil in clinical trails, the adverse reactions were generally transient and mild to moderate in nature. The most commonly reported adverse drug reactions occurring in ≥ 10 % of patients are headache and flushing.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness The following adverse reactions have been reported:

*For adverse reactions reported in <1% of patients, only those which warrant special attention, because of their possible association with serious disease states or of otherwise clinical relevance are listed.
*Sudden deafness or loss of hearing has been reported in a small number of post-marketing and clinical trial cases with the use of all PDE5 inhibitors, including vardenafil.
At the 20 mg dose, elderly (≥ 65 years old) patients had higher frequencies of headaches (16.2% versus 11.8%) and dizziness (3.7% versus 0.7%) than younger patients (<65 years old).
Post marketing reports of another medicinal product of this class: 
Vascular Disorders: serious cardiovascular events, including cerebrovascular hemorrhage, sudden cardiac death, transient ischemic attack, unstable angina and ventricular arrhythmia have been reported post marketing in temporal association with another medicinal product in this class.
4.9 Overdose
In single dose volunteer studies, doses up to and including 80 mg per day were tolerated without exhibiting serious adverse reactions.
When vardenafil was administered in higher doses and more frequently than the recommended dosing regimen (40 mg twice daily) cases of severe back pain have been reported. This was not associated with any muscle or neurological toxicity.
In cases of overdose, standard supportive measures should be adopted 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.

Pharmacotherapeutic group: Medicinal product used in erectile dysfunction, ATC code: G04BE09
Vardenafil is an oral therapy for the improvement of erectile function in men with erectile dysfunction, in the natural setting, i.e. with sexual stimulation it restores impaired erectile function by increasing blood flow to the penis.
Penile erection is a haemodynamic process. During sexual stimulation, nitric oxide is released, it activates the enzyme guanylatecyclase, resulting in an increased level of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. This in turn results in smooth muscle relaxation, allowing increased inflow of blood into the penis. The level of cGMP is regulated by the rate of synthesis via guanylatecyclase and by the rate of degradation via cGMP hydrolyzing phosphadiesterases (PDEs)
Vardenafil is a potent and selective inhibitor of the cGMP specific phosphadiesterases type 5 (PDE5), the most prominent PDE in the human corpus cavernosum. Vardenafil potently enhances the effect of endogenous nitric oxide in the corpus cavernosum by inhibiting PDE5.
When nitric oxide is released in response to sexual stimulation, inhibition of PDE5 by vardenafil results in increased corpus cavernosum levels of cGMP, sexual stimulation is therefore required for vardenafil to produce its beneficial therapeutic effects.

Absorption
Vardenafil is rapidly absorbed with maximum observed plasma concentration reached in some men as early as 15 minutes after oral administration. However 90% of the time, maximum plasma concentration are reached within 30-120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 15 %.  After oral dosing of vardenafil AUC and Cmax increase almost dose proportionally over the recommended dose rang (5 – 20 mg).
When vardenafil is taken with a high fat meal (containing 57% fat), the rate of absorption is reduced, with an increase in the median tmax of 1 hour and a mean reduction in Cmax of 20% vardenafil AUC is not affected. After a meal containing 30% fat, the rate and extent of absorption of vardenafil (tmax, Cmax and AUC) are unchanged compared to administration under fasting conditions.
Distribution
The mean steady state volume of distribution for vardenafil is 208 l, indicating distribution into the tissues. Vardenafil and its major circulating metabolite (M1) are highly bound to plasma proteins (approximately 95% for vardenafil or M1). For vardenafil as well as M1, protein binding is independent of total drug concentration. Based on measurements of vardenafil in semen of healthy subjects 90 minutes after dosing, not more than 0.00012% of the administered dose may appear in the semen of patients.
Metabolism
Vardenafil is metabolized predominantly by hepatic metabolism via cytochrome P450 (CYP) isoform 3A4 with some contribution from CYP3A5 and CYP2C isoform. In humans the one major circulating metabolite (M1) results from desethylation of vardenafil and is subject to further metabolism with a plasma elimination half-life of approximately 4 hours. Parts of M1 are in the form of the glucuronide in systemic circulation. Metabolite M1 shows a phosphodiesterase selectivity profile similar to vardenafil and an in vitro potency for phosphodiesterase type 5 of approximately 28% compared to vardenafil, resulting in an efficacy contribution of about 7%.
Elimination
The total body clearance of vardenafil is 56 l/h with a resultant terminal half-life of approximately 4–5 hours. After oral administration, vardenafil is excreted as 
metabolites predominantly in the faeces (approximately 91 – 95 % of the administered dose) and to a lesser extent in the urine, (approximately 2–6% of the administered dose). 
Pharmacokinetics in special patient groups:
Elderly
Hepatic clearance of vardenafil in healthy elderly volunteers (65 years and over) was reduced as compared to healthy younger volunteers (18-45 years). 
On average elderly males had a 52% higher AUC, and a 34% higher Cmax than younger males (see section 4.2).
Renal insufficiency
In volunteers with mild to moderate renal impairment (creatinine clearance 30 – 80 ml/min), the pharmacokinetics of vardenafil were similar to that of a normal
renal function control group. In volunteers with severe renal impairment (creatinine clearance < 30 ml/min) the mean AUC was increased by 21% and the mean Cmax decreased by 23% compared to volunteers with no renal impairment. No statistically significant correlation was observed between creatinine clearance and vardenafil exposure (AUC and Cmax) (see section 4.2). Vardenafil Pharmacokinetics has not been studied in patients requiring dialysis (see section 4.3).
Hepatic insufficiency
In patients with mild to moderate hepatic impairment (Child – Pugh A and B), the clearance of vardenafil was reduced in proportion to the degree of hepatic impairment. In patients with mild hepatic impairment (Child – Pugh A), the mean AUC and Cmax increased 17% and 22% respectively, compared to healthy control subjects. 
In patients with moderate impairment (Child – Pugh B), the mean AUC and Cmax increased160% and 133% respectively, compared to healthy control subjects 
(see section 4.2).
The Pharmacokinetics of vardenafil in patients with severely impaired hepatic function (Child – Pugh C) has not been studied (see section 4.3).

Crosscarmellose sodium, hydroxyl propyl cellulose, lactose monohydrate, avicel ph 101, magnesium stearate, hypromellose, talc, titanium dioxide, triacetin.

Store at a temperature not exceeding 30 o C, in a dry place.

A carton box containing 1 (AL/PVC) contains 4 Tablets and an insert leaflet