lovex registr (2)

Specification

Lovex, 100 mg Tablets

Tests Specifications References

Appearance White or off white tablets with

facet and breakline on one side.

Visual inspection

Identification

1) HPLC

2) Reaction on citrates

1) The retention time of the

standard solution main peak and

the test solution main peak should

be essentially identical.

2) Gives reactions of citrates

Ph.Eur. 2.2.29.

Ph.Eur. 2.3.1.

Average weight and

uniformity of weight (by

weight variation)

600.0 mg 5 % Ph.Eur. 2.9.5.

Disintegration NMT 15 minutes Ph.Eur. 2.9.1.

Friability NMT 0.1 % Ph.Eur. 2.9.7.

Dissolution NMT 75 % of labeled amount of

Sildenafil Citrate in 45 minutes

Ph.Eur. 2.9.3.

Related substance (HPLC) Any impurity NMT 1.0 %

Total impurity NMT 2.0 %

Ph.Eur. 2.2.29.

Microbial contamination

Total aerobic count

Fungi

E. Coli

NMT 1000 cfu/g

NMT 00 cfu/g

Absent/g

Ph.Eur. 5.1.4.

Assay From 90.0 % to 110 % Ph.Eur. 2.2.29.

Analytical Methods

Appearance.

White or off white tablets with facet and breakline on one side.

Identification

1) Using method given under Assay by HPLC, the retention time of the standard solution main

peak and the test solution main peak should be essentially identical.

2) Crush 20 tablets to the powder. Dissolve 0.5 mg of this powder in 10 ml of water R, filter

through paper. Add 3 ml of 200 g/l calcium chloride solution to 1 ml of filtrate and boiled. The white

residue formed, which resolves after cooling (Ph. Eur. 2.3.1).

Average weight and uniformity of weight (Ph. Eur. 2.9.5.)

600 mg 5 %

Weigh individually 20 tablets taken at random and determine the average mass. Not more than 2 of

the individual masses deviate from the average mass by more than 5 % and none deviates by more

than twice that percentage.

Disintegration ( Ph. Eur. 2.9.1.)

Must comply with test for uncoated tablets. Use water R at 37 2 C temperature. Add a disc to each

tube. Operate the apparatus for 15 min and examine the state of the tablets. If the tablets fail to

comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets

omitting the discs.

Friability ( Ph. Eur. 2.9.7.)

Take a sample of whole tablets corresponding as near as possible to 6.0 g. The tablets are carefully

dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum.

Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before,

and accurately weigh.

Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the

tablet sample after tumbling, the sample fails the test. If the results are difficult to interpret or if the

weight loss is greater than the targeted value, the test is repeated twice and the mean of the 3 tests

determined. A maximum loss of mass (obtained from a single test or from the mean of 3 tests) not

greater than 1.0 per cent is considered acceptable for the tablet.

Dissolution

Dissolution conditions

Apparatus : Type II (Padle)

Dissolution medium : 500 ml, 0.1 M HCl

Rate : 100 rpm

Time : 45 minutes

Method: Spectrophotometric (Ph. Eur. 2.2.25.)

Test solution:

Place one tablet in each vessel and carry out the method according to Ph. Eur. 2.9.3. After 45

minutes, pipette 25 ml of the solution from each vessel. Filter the solution through a suitable

membane fiber filer (diameters of pores 0.45 m), disregarding the first 5 ml. Dilute 5.0 ml of this

solution to 50.0 ml with 0.1 M HCl.

Standard solution:

Transfer approximately 14 mg of Sildenafil citrate WS, accurately weighed into a 10 ml volumetric

flask. Dissolve with sufficient volume (app. 5 ml) of 0.1 M HCl and dilute to the volume with the

same solvent. Pipette 1 ml of this solution a 50 ml volumetric flask. Dilute to the volume with 0.1 M

HCl. Protect solution from light.

Procedure:

Measure the absorbance values of the solutions using 0.1 M HCl as a blank at 290 nm wavelight.

Calculation:

D1 m0 500 50 P100 0.7129 D1 m0 P 1.4258

= --------------- -------------------------------------- = ---------------------------- D0 a 50 50 5 100 D0 a

D0 The absorbance value of Test Solution

D1 The absorbance value of Standard solution;

m0 Weigh of Sildenafil citrate WS, in mg;

a labeling amount of Sildenafil, mg;

P Potency of Sildenafil citrate WS , %,

0.7129 Conversation coefficient of Sildenafil citrate to Sildenafil

Limit: Not less than 75 % of the labeled amount of Sildenafil is dissolved in 45 minutes.

Related substance (HPLC, Ph. Eur. 2.2.29.)

Proceed as described in Assay.

Test solution (a):

Powder 10 tablets finely. Transfer 300 mg of the tablet powder (equivalent to 50 mg of Sildenafil) to

a 100 ml volumetric flask, add 70 ml of mobile phase, shake with mechanical shaker. Dilute to

volume with the same solvent and mix. Pipette 5 ml of this solution into 10 ml volumetric flask.

Dilute to the volume with mobile phase.

Test solution (b):

Dilute 1.0 ml of the test solution (a) to 100 ml the mobile phase.

Evaluations:

In the chromatogram obtained with the test solution (a):

1. The area of any peak is not greater than the area of the principal peak in the chromatogram

obtained with the test solution (b) (1.0 per cent)

2. The sum of the areas of all the peaks, apart from the principal peak is not greater than 2 times

the area of the principal peak in the chromatogram obtained with the test solution (b) (2.0 per

cent).

Calculation:

r1 100

-------------------- ------ = Individual impurity, %

rt r1 The peak area of the individual impurity obtained from the test solution (a);

rt The total peak apart from the mobile phase obtained from the test solution (a).

Microbial contamination (Ph. Eur. 5.1.4.)

Total viable aerobic count. Not more than 103 aerobic bacteria and not more than 10

2 fungi per gram.

Absence of Escherichia coli (1 g).

Assay (HPLC, Ph. Eur. 2.2.29.)

Chromatographic conditions:

Apparatus : High Pressure Liquid Chromatography

Column : C18, 15 cm 4.0 mm, 5 m, temperature 30 C

Detector : UV, 290 nm

Flow rate : 1.0 ml/min

Injection volume : 15 l

Mobile phase : filtered and degassed phosphate buffer pH 3.0 methanol

acetonitrile (58:25:17)

Pump : Isocratic

Test solution:

Powder 20 tablets finally. Transfer 510 mg of the tablet powder to a 100 ml volumetric flask. Add 10

ml of Acetonitrile : water mixture (9:1 v/v), sonicate for 10 minutes, add sufficient volume of mobile

phase and sonicate 10 minutes. Shake with a mechanical shaker for 30 minutes. Dilute to the volume

with the mobile phase, centrifuge at 8000 rpm during 5 minutes.

Test solution (a):

Transfer 0.1 g of Sildenafil citrate WS to a 100 ml volumetric flask, add 70 ml of mobile phase.

Dilute to volume with the mobile phase and mix.

Phosphate buffer pH 3.0:

Transfer 7 ml of Triethylamine into 1000 ml volumetric flask consisting 900 ml of water R. Mix and

adjust pH to 3.0 with phosphoric acid. Dilute to the volume with water.

Calculation:

S1m0100P1000 S1m0 P10

(Sildenafil/Tablet)=----- ---------- ----------------- b = -------------------- b, S0 m1100 100 S0 m1

where

S1 The peak area of Sildenafil citrate obtained from the test solution;

S0 The peak area of Sildenafil citrate obtained from the standard solution;

m0 Weight of Sildenafil citrate WS, in mg;

m1 Weight of sample, in mg;

b Average weight of tablets, in mg;

P Potency of Sildenafil citrate WS, in %.

Limit: From 90.0 % to 110.0 % of Sildenafil (C22H30N6O4S) in tablet.

Presentation.

100 mg tablets. Blister of 1x4 tablets in a carton box with a leaflet.

Labeling.

On primary packaging name of manufacturer, manufacturing country, name of customer and its

requisites, name of pharmaceutical product, INN, dosage, batch N, expire date.

On secondary packaging - name of manufacturer, manufacturing country, name of customer and its

requisites, name of pharmaceutical product, INN, dosage, dosage form, storage, batch N, quantity in

packaging, +expire date, bar code.

Storage. Store at a dry place at temperature below 25 C. Protect from light.

Shelf-Life. 2 years. Do not use after the expiry date printed on the pack.

Pharmacotherapeutic Group. Drugs used in erectile dysfunction.

LOVEX Diagram 1: Flow Diagram of Manufacturing Process for tablets batch

#40 mesh Colloidal Silicon Dioxide USP/NF

SS Screen ( SS Screen (Aerosil 200)

Microcrystalline Cellulose Ph. Eur.

Materials from sifting step

Tumbler bin; 200 l Mannitol ,

30 minutes; 20 rpm Sildenafil Citrate USP,

Zinc Citrate dihydrate

Tumbler bin; 200 l #40 mesh Magnesium Stearate USP/NF 5 minutes; 20 rpm SS Screen

Tablet press Tablet weight: 600mg (570-630)

Hardness: 20-25 kgf

Blister packaging machine Blister of 1x4 tablets, 100 mg/tab

Quality control product

Sifting

Final Blend

Compression

Pre-Mix

Packaging

Finished Product

Sifting

Manufacturing

Master Manufacturing Formula:

BATCH SIZE: 80 000 Tablets

Name of the Ingredient Specifications Overages (%) Qty. /Batch (%)

Active Ingredients

1. Sildenafil Citrate USP NIL 21.6

In-Active Ingredients

2. Microcrystalline cellulose Ph. Eur. NIL 16.7

3. Zinc acetate dihydrate Ph. Eur./USP NIL 1.7

4. Aerosil USP/NF NIL 1.0

5. Mannitol Ph. Eur./USP NIL 58.0

6. Magnesium stearate Ph. Eur. NIL 1.0

MANUFACTURING PROCESS

OF

LOVEX

Sildenafil Tablets 100 mg

Method of Manufacture

All the operations are carried out in a clean area following good manufacturing practices and

under controlled conditions of temperature and humidity.

Line clearance:

Before manufacturing operation is begun:

All machineries and equipment used for manufacturing process are cleaned as per respective

standard operating procedure for cleaning.

The manufacturing area to be used is cleaned and made suitable for operations.

All the process, products name are properly displayed in notified area.

Safety gadgets like hand gloves, mask and slippers provided to workmen.

List of Equipments:

SS Screen

Sifter

Sieves

Tumbler bin

Tablet press

Blister packaging machine

OPERATIONAL PROCEDURE

Issue intimation slip to Q. A. D. for Swab Test / Wash Water Analysis & D. M. water analysis.

After getting approval (Line Clearance) from Q. A. D. start the procedure as follows.

1. WEIGHING:

Weigh accurately all the active and inactive ingredients. Recheck the weight of dispensed

materials received from stores.

2. SIFTING:

Sift Sildenafil Citrate USP, Colloidal Silicon Dioxide (Aerosil) USP/NF, Microcrystalline

Cellulose Ph. Eur., Mannitol Ph.Eur./USP, Zinc Acetate Dihydrate Ph.Eur./USP, and Magnesium

Stearate Ph.Eur. through sifter using 40 # sieve in In process container (IPC).

3. PRE- MIXING:

Take Aerosil, Microcrystalline Cellulose sift together then put to the 200 l tumbler bin along

with Mannitol, Sildenafil Citrate and Zinc Citrate Dihydrate. Mix during 30 min at 20 rpm.

4. FINAL BLEND:

Put Magnesium Stearate to the ready mix in the 200 l tumbler bin and mix for 5 min at 20 rpm.

5. COMPRESSION

Carry the IPC Container to the compression cubicle using trolley.

Mount the IPC content on the hopper of 27 station double rotary compression machine.

Adjust parameters as given in In process check and test the parameters for individual punch.

Discard the tablets obtained during trial run and put in SS bin for rejected materials.

The parameters if within limits compress the tablets and collect in capacity IPCs with proper

labeling.

In-process control Tablet average weight 600 mg 5% (570 mg 630 mg); Hardness 20-25 kgf.

6. VISUAL INSPECTION:

Visual inspection of the tablets is done & good tablets are stored.

7. OVERPRINTING DETAILS:

Print the required details on the Cartons & Box Labels.

8. PACKING (BLISTER PACKING)

To be packed as per the Standard Packing Specification.

9. STORAGE

Store below 25 C in a dry place. Protect from light.

1

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

FOR

3 BATCHES STORED AT ROOM TEMPERATURE

25C ( 2C) AND RELATIVE HUMIDITY 60% ( 5%)

Stability studies were carried out on the three following batches of Lovex (100 mg tablets #4)

Batch No. LV010612 LV020612 LV030612

Mfg. Date 01/06/2012 02/06/2012 03/06/2012

Expiry Date 01/06/2014 02/06/2014 03/06/2014

The 3 batches are stored in the commercial packaging.

(Alu-PVC blister pack of 10 tablets. Blister of 1x4 tablets in a carton box with a leaflet.)

2


Product Name : Lovex

Generic Name : Sildenafil

Contents : Each tablet contains:

Sildenafil (as citrate) 100 mg; excipients: microcrystalline cellulose, zinc citrate

dihydrate, aerosol, mannitol, magnesium stearate.

Batch No. : LV010612

Batch size : 1 000 Tablets

Manufacturing Date : 01/06/2012

Expiry Date : 01/06/2014

Storage Conditions : Store at temperature 40C ( 20C ) & Relative

Humidity 75% ( 5%)

Pack Size : Alu-PVC blister pack of 4 Tablets

Description : White to off white colored, round-shaped, flat, bevelled

edge, uncoated tablets with score mark on one side.

Identification : A: TLC

B: The retention times of the major peaks in the

chromatogram of the Assay preparation correspond to

those in the chromatogram of the Standard preparation,

as obtained in the Assay.

Average weight of tablet : 600 mg 5%

Disintegration time :

NMT 15.0 min

Grateness of tablets :

NMT 1.0%

Dissolution :

NLT 75% of Active Ingredient dissolved in 45 minutes

Related substances :

Individual NMT 0.5% total NMT 1.0%

Microbial limit test

:

Not more than 1000 cfu/gm total aerobic microbial

count.

Not more than 100 cfu/gm for yeast & mold,

Escherichia coli absent.

Assay :

90110 mg

Analytical Method : As per USP, Ph. Eur., Inhouse

3


Tests Limits

Results of Analysis

0

12.06.12

3

10.09.12

6

10.12.13

Description White to off white colored, round-shaped,

flat, bevelled edge, uncoated tablets with

score mark on one side.

Complies Complies Complies

Identification

Positive Positive Positive Positive

Average weight of tablet and

Uniformity of weight 600.0 mg 5 % (570.0630.0) mg 615 mg 611 mg 602 mg

Disintegration time NMT 15.0 min 5.0 min 8 min 7 min

Grateness of tablets NMT 1.0% 1.0% 1.0% 1.0%

Dissolution NLT 75% 95% 81% 79%

Related substances Individual NMT 0.5% total NMT 1.0%



Not more than 1000 cfu/gm total aerobic

microbial count

Not more than 100 cfu/gm for yeast &

mold, Escherichia coli absent.


Assay 90110 mg 105 mg/tab 101 mg/tab 103 mg/tab

Discussion: The results show that there are no significant physical or chemical changes when the product is kept at a temperature of 25C

2C and relative humidity 60% 5 % for 12 months. Remarks: The above product is stable for a period of 24 months.

4












Humidity 75% ( 5%)











NMT 15.0 min


NMT 1.0%

Dissolution :





:


count.



Assay :

90110 mg


5


Tests Limits

Results of Analysis

0

12.06.12

3

10.09.12

6

10.12.13





Identification




Disintegration time NMT 15.0 min 7.0 min 6.0 min 5.0 min







microbial count





Discussion: The results show that there are no significant physical or chemical changes when the product is kept at a temperature of 25C

2C and relative humidity 60% 5 % for 12 months. Remarks: The above product is stable for a period of 24 months.

6












Humidity 75% ( 5%)











NMT 15.0 min


NMT 1.0%

Dissolution :





:


count.



Assay :

90110 mg


7


Tests Limits

Results of Analysis

0

12.06.12

3

10.09.12

6

10.12.13





Identification




Disintegration time NMT 15.0 min 8.0 wT 5.0 wT 6.0 wT







microbial count





Discussion: The results show that there is no significant physical or chemical changes when the product is kept at a temperature of 400C (

20C ) and Relative Humidity 75% ( 5%) for 6 months.

Remarks: The 24 months expiration period is supported by the available stability study performed under accelerated conditions (40C

2C/75% RH 5%RH) for 6 months.

LOVEX Diagram 1: Flow Diagram of Manufacturing Process for tablets batch

#40 mesh Colloidal Silicon Dioxide NF

SS Screen (Aerosil 200)

microcrystalline cellulose

Materials from sifting step

Tumbler bin; 200L Mannitol,

30 minutes; 20 rpm Sildenafil Citrate,

zinc citrate dihydrate

Tumbler bin; 200L #40 mesh Magnesium stearate, NF 5 minutes; 20 rpm SS Screen

Tablet press Tablet weight: 600 mg (570-630)

Hardness: 20-25 kgf

Blister packaging machine Blister of 1x4 tablets, 100mg/tab

Quality control product

Sifting

Final Blend

Compression

Pre-Mix

Packaging

Finished Product

Sifting

Specification

Lovex, 100 mg Tablets

Tests Specifications References

Appearance White or off white tablets with

facet and breakline on one side.

Visual inspection

Identification

1) HPLC

2) Reaction on citrates

1) The retention time of the

standard solution main peak and

the test solution main peak should

be essentially identical.

2) Gives reactions of citrates

Ph.Eur. 2.2.29.

Ph.Eur. 2.3.1.

Average weight and

uniformity of weight (by

weight variation)

600.0 mg 5 % Ph.Eur. 2.9.5.

Disintegration NMT 15 minutes Ph.Eur. 2.9.1.

Friability NMT 0.1 % Ph.Eur. 2.9.7.

Dissolution NMT 75 % of labeled amount of

Sildenafil Citrate in 45 minutes

Ph.Eur. 2.9.3.

Related substance (HPLC) Any impurity NMT 1.0 %

Total impurity NMT 2.0 %

Ph.Eur. 2.2.29.

Microbial contamination

Total aerobic count

Fungi

E. Coli

NMT 1000 cfu/g

NMT 00 cfu/g

Absent/g

Ph.Eur. 5.1.4.

Assay From 90.0 % to 110 % Ph.Eur. 2.2.29.

Analytical Methods

Appearance.

White or off white tablets with facet and breakline on one side.

Identification

1) Using method given under Assay by HPLC, the retention time of the standard solution main

peak and the test solution main peak should be essentially identical.

2) Crush 20 tablets to the powder. Dissolve 0.5 mg of this powder in 10 ml of water R, filter

through paper. Add 3 ml of 200 g/l calcium chloride solution to 1 ml of filtrate and boiled. The white

residue formed, which resolves after cooling (Ph. Eur. 2.3.1).

Average weight and uniformity of weight (Ph. Eur. 2.9.5.)

600 mg 5 %

Weigh individually 20 tablets taken at random and determine the average mass. Not more than 2 of

the individual masses deviate from the average mass by more than 5 % and none deviates by more

than twice that percentage.

Disintegration ( Ph. Eur. 2.9.1.)

Must comply with test for uncoated tablets. Use water R at 37 2 C temperature. Add a disc to each

tube. Operate the apparatus for 15 min and examine the state of the tablets. If the tablets fail to

comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets

omitting the discs.

Friability ( Ph. Eur. 2.9.7.)

Take a sample of whole tablets corresponding as near as possible to 6.0 g. The tablets are carefully

dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum.

Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before,

and accurately weigh.

Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the

tablet sample after tumbling, the sample fails the test. If the results are difficult to interpret or if the

weight loss is greater than the targeted value, the test is repeated twice and the mean of the 3 tests

determined. A maximum loss of mass (obtained from a single test or from the mean of 3 tests) not

greater than 1.0 per cent is considered acceptable for the tablet.

Dissolution

Dissolution conditions

Apparatus : Type II (Padle)

Dissolution medium : 500 ml, 0.1 M HCl

Rate : 100 rpm

Time : 45 minutes

Method: Spectrophotometric (Ph. Eur. 2.2.25.)

Test solution:

Place one tablet in each vessel and carry out the method according to Ph. Eur. 2.9.3. After 45

minutes, pipette 25 ml of the solution from each vessel. Filter the solution through a suitable

membane fiber filer (diameters of pores 0.45 m), disregarding the first 5 ml. Dilute 5.0 ml of this

solution to 50.0 ml with 0.1 M HCl.

Standard solution:

Transfer approximately 14 mg of Sildenafil citrate WS, accurately weighed into a 10 ml volumetric

flask. Dissolve with sufficient volume (app. 5 ml) of 0.1 M HCl and dilute to the volume with the

same solvent. Pipette 1 ml of this solution a 50 ml volumetric flask. Dilute to the volume with 0.1 M

HCl. Protect solution from light.

Procedure:

Measure the absorbance values of the solutions using 0.1 M HCl as a blank at 290 nm wavelight.

Calculation:

D1 m0 500 50 P100 0.7129 D1 m0 P 1.4258

= --------------- -------------------------------------- = ---------------------------- D0 a 50 50 5 100 D0 a





P Potency of Sildenafil citrate WS , %,


Limit: Not less than 75 % of the labeled amount of Sildenafil is dissolved in 45 minutes.

Related substance (HPLC, Ph. Eur. 2.2.29.)

Proceed as described in Assay.

Test solution (a):

Powder 10 tablets finely. Transfer 300 mg of the tablet powder (equivalent to 50 mg of Sildenafil) to

a 100 ml volumetric flask, add 70 ml of mobile phase, shake with mechanical shaker. Dilute to

volume with the same solvent and mix. Pipette 5 ml of this solution into 10 ml volumetric flask.

Dilute to the volume with mobile phase.

Test solution (b):

Dilute 1.0 ml of the test solution (a) to 100 ml the mobile phase.

Evaluations:

In the chromatogram obtained with the test solution (a):

1. The area of any peak is not greater than the area of the principal peak in the chromatogram

obtained with the test solution (b) (1.0 per cent)

2. The sum of the areas of all the peaks, apart from the principal peak is not greater than 2 times

the area of the principal peak in the chromatogram obtained with the test solution (b) (2.0 per

cent).

Calculation:

r1 100

-------------------- ------ = Individual impurity, %

rt r1 The peak area of the individual impurity obtained from the test solution (a);

rt The total peak apart from the mobile phase obtained from the test solution (a).

Microbial contamination (Ph. Eur. 5.1.4.)

Total viable aerobic count. Not more than 103 aerobic bacteria and not more than 10

2 fungi per gram.

Absence of Escherichia coli (1 g).

Assay (HPLC, Ph. Eur. 2.2.29.)

Chromatographic conditions:

Apparatus : High Pressure Liquid Chromatography

Column : C18, 15 cm 4.0 mm, 5 m, temperature 30 C

Detector : UV, 290 nm

Flow rate : 1.0 ml/min

Injection volume : 15 l

Mobile phase : filtered and degassed phosphate buffer pH 3.0 methanol

acetonitrile (58:25:17)

Pump : Isocratic

Test solution:

Powder 20 tablets finally. Transfer 510 mg of the tablet powder to a 100 ml volumetric flask. Add 10

ml of Acetonitrile : water mixture (9:1 v/v), sonicate for 10 minutes, add sufficient volume of mobile

phase and sonicate 10 minutes. Shake with a mechanical shaker for 30 minutes. Dilute to the volume

with the mobile phase, centrifuge at 8000 rpm during 5 minutes.

Test solution (a):

Transfer 0.1 g of Sildenafil citrate WS to a 100 ml volumetric flask, add 70 ml of mobile phase.

Dilute to volume with the mobile phase and mix.

Phosphate buffer pH 3.0:

Transfer 7 ml of Triethylamine into 1000 ml volumetric flask consisting 900 ml of water R. Mix and

adjust pH to 3.0 with phosphoric acid. Dilute to the volume with water.

Calculation:

S1m0100P1000 S1m0 P10

(Sildenafil/Tablet)=----- ---------- ----------------- b = -------------------- b, S0 m1100 100 S0 m1

where

S1 The peak area of Sildenafil citrate obtained from the test solution;

S0 The peak area of Sildenafil citrate obtained from the standard solution;

m0 Weight of Sildenafil citrate WS, in mg;

m1 Weight of sample, in mg;

b Average weight of tablets, in mg;

P Potency of Sildenafil citrate WS, in %.

Limit: From 90.0 % to 110.0 % of Sildenafil (C22H30N6O4S) in tablet.

Presentation.


Labeling.

On primary packaging name of manufacturer, manufacturing country, name of customer and its

requisites, name of pharmaceutical product, INN, dosage, batch N, expire date.

On secondary packaging - name of manufacturer, manufacturing country, name of customer and its

requisites, name of pharmaceutical product, INN, dosage, dosage form, storage, batch N, quantity in

packaging, +expire date, bar code.

Storage. Store at a dry place at temperature below 25 C. Protect from light.

Shelf-Life. 2 years. Do not use after the expiry date printed on the pack.

Pharmacotherapeutic Group. Drugs used in erectile dysfunction.

In Vitro Bioequvalence Study for Lovex (Sildenafil 100 mg tablets)

manufactured by PharmImpEx (Georgia) vs Viagra (Sildenafil 100 mg

tablets) manufactured by Pfizer PMG (France)

Sponsor - SKR, georgia

Introduction

Lovex (Sildenafil 100 mg tablet) is a generic medicinal product containing sildenafil as an

active substance.

Lovex contains the same active substance as the reference medicinal product (Viagra) -

sildenafil in form of the citrate salt.

Sildenafil is potent inhibitor of cyclic guanosine monophosphate (cGMP) specific

phosphodiesterase (PDE5). During natural erection, nitric oxide (NO) is released and this triggers the

synthesis of cGMP which, in turn, relaxes the corpora cavernosa (a key point in the erection process).

PDE5 present in the corpus cavernosum breaks down cGMP, sildenafil prevents the breakdown of

cGMP and, thus enhances the induced erectile response. Sildenafil has a high potency and selectivity

for PDE5 and via smooth muscle relaxation can induce a rise in intracavernosal pressure during

stimulation.

The safety and efficacy profile of sildenafil has been demonstrated in several clinical trials

details of which can be found in the EPAR for Viagra. In addition, there is a long-term post-marketing

experience contributing to the knowledge of the use of this product. Since this application is a generic

application referring to the reference medicinal product Viagra, summary of the clinical data of

sildenafil citrate is available and no new clinical studies regarding pharmacology, pharmacokinetics

and efficacy and safety have been conducted.

The indication for Lovex is the same as for reference medicinal product. Lovex is indicated for

the treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile

erection sufficient for satisfactory sexual performance. In order for sildenafil to be effective, sexual

stimulation is required.

Lovex is presented as uncoated tablets containing 100 mg of sildenafil (active substance). The

active substance is in form of citrate salt. Excipients used in the preparation of Lovex are well known

excipients used in tablets preparations such as microcrystalline cellulose, zinc citrate dihydrate, aerosol,

mannitol, magnesium stearate.

Active Substance

The active substance, sildenafil citrate, is chemically designated as 5-[2-Ethoxy-5-(4-

methylpiperazin-1-ylsulfonyl)phenyl]-1,6-dihydro-1-methyl-3-propylpyrazolo[4,3-d]pyrimidin-7-one

citrate; 1-{[3-6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-

ethoxyphenyl]sulfonyl}-4-methylpiperazone citrate. It does not show polymorphism or enantiomerism.

Sildenafil citrate was originally approved in 1998 as an oral formulation for the treatment of

erectile dysfunction. It is a potent and specific inhibitor of phosphodiesterase type 5 which enhances

vasodilation by inhibiting the catabolism of cyclic guanosine monophosphate (GMP).

The solubility of sildenafil citrate in water has been determinate as being 3.5 mg/ml. Solubility

determinations in various buffers showed a maximum solubility of approximately 24 mg/ml at pH 2.0.

Sildenafil citrate is designated as a class 1 drug substance according to BCS classification:

highly soluble and highly permeable.

Biowaiver is a regulatory drug approval process when generic drug interchangeability is

established based on biopharmaceutical properties an in vitro equivalence test instead of in vivo

bioequivalence studies.

In vitro equivalence test is a dissolution test that includes comparison of the dissolution profile

between the test and reference product (or different doses of the same drug product) in three media: pH

1.2, pH 4.5 and pH 6.8.

In vitro equivalence report for generic drugs according biowaiver procedure includes:

1. Aims of study

The main aim of study is to establish generic drugs interchangeability that can be proved by in

vitro dissolution kinetics study, which is performed instead of in vivo bioequivalence studies.

2. Information about reference and test product

Reference product: Viagra, 100 mg tablets

Test product: Lovex, 100 mg tablets

3. Dissolution kinetics study conditions, assay procedure conditions and results of study

This is a test intended for evaluation of dissolution profiles similarity when the quantity of API

released is assayed in three or more previously chosen time points and in three different media: pH 1.2,

pH 4.5, pH 6.2. and pH 6.8.

Bioequivalence study was performed on the 100 mg strength in accordance with the Note for

Guidance on the Investigation of Bioavailability and Bioequivalence - World Health Organization

(WHO) Proposal to waive in vivo bioequivalence requirements for the WHO model list of essential

medicines immediate release, solid oral dosage forms. Working document QAS/04.109/Rev.1.

Methods of dissolution kinetics study

Presentation

Dissolution test was conducted on 12 dosage units of the test product Lovex, 100 mg tablets,

PharmImpEx (Georgia), versus 12 dosage units of the reference product, Viagra, 100 mg, tablets,

Pfizer PGM, France.

The current official USP dissolution test conditions and acceptance criterion were applied. The

following method and tolerances were applied: the dissolution of sildenafil citrate from its tablets was

performed according to the rotating basket method using a USP dissolution tester, apparatus II

(Erweka) in 500 ml of three (3) different buffers (pH 1.2 (HCl buffer) pH 4.5 (acetate buffer) and pH

6.8 (phosphate buffer). All buffers are prepared as per USP requirement. The stirring speed was 100

rpm and the temperature was maintained at 37 0.5 C. Aliquots each of 25 ml from the dissolution

medium were withdrawn at 10, 15, 20, 30 and 45 minutes time intervals. The samples withdrawn were

then filtered, adequately diluted and analyzed spectrophotometrically for sildenafil citrate content by

measuring the absorbance at max - 290 nm (UV-1601 PC, Shimadzu, Japan). A similar volume of

buffers respectively was added to the dissolution medium in order to maintain the volume in the vessel

constant. Each experiment was carried out in triplicate.

Test product - Lovex, 100 mg tablets, manufactured by PharmImpEx, Georgia.

Referense product Viagra, 100 mg tabletebi (Batch N 0752702), manufacturer Pfizer PGM,

France.

12-12 tablets were used in study.

Test solution:

Place one tablet in each vessel and carry out the method according to USP method After , 15, 20,

30 and 45 minutes time intervals, pipette 25 ml of the solution from each vessel. Filter the solution

through a suitable membane fiber filer (diameters of pores 0.45 m), disregarding the first 5 ml. Dilute

5.0 ml of this solution to 50.0 ml with 0.1 M HCl.

Standard solution:

Transfer approximately 14 mg of Sildenafil citrate WS, accurately weighed into a 10 ml

volumetric flask. Dissolve with sufficient volume (app. 5 ml) of 0.1 M HCl and dilute to the volume

with the same solvent. Pipette 1 ml of this solution a 50 ml volumetric flask. Dilute to the volume with

0.1 M HCl. Protect solution from light.

Procedure:

Measure the absorbance values of the solutions using appropriate buffer as a blank at 290 nm

wavelight.

Calculation:

D1 m0 500 50 P100 0.7129 D1 m0 P 1.4258

= -------------- -------------------------------------- = ---------------------------- (1) D0 a 50 50 5 100 D0 a





P Potency of Sildenafil citrate WS, %,


Statistical analysis

All statistical analyses were made using ANOVA, followed by Fishers PLSD (pair- wise least

significant difference) for multiple comparisons at p 0.05 using the StatView statistical software

program.

Results of In vitro dissolution studies

In vitro dissolution studies of test tablets containing 100 mg of Sildenafil together with the

conventional market product Viagra 100 mg oral tablets (Pfizer, France).

Dissolution profiles of the prepared 12-12 tablets were compared with the commercial product using

the similarity factor (2) defined by the following equation (2):

f2 = 50log [

] (2)

where n is the number of sampling time points, R(t) and T(t) are the mean percent dissolved of the

reference (commercial product) and the test (prepared tablets), respectively, up to each time point t. 2

represents a logarithmic transformation of the sum squared error of differences between the reference

and the test products over all time points. In order to consider similar dissolution profiles, 2 values

should be higher than 50. According to literature studies, similarity factor f2 value is 50 to 100.

Concerning, the experimental values for the simi1arity factor f2 obtained are grater that 50 and lower

than 100 and that indicates that the drugs achieve similar dissolution profiles.

Table 1. Dissolution rate (%) of Lovex (100 mg Tablets, manufacturer PharmImpEx, Georgia)

(T) and Viagra (100 mg Tablets, manufacturer Pfizer PGM, France) (R) in different buffers

during 45 min.

10 min 15 min 20 min 25 min 30 min 45 min

pH 1.2

T 38 51 68 76 89 99

R 40 58 73 82 93 100

pH 4.5

T 31 50 66 76 83 90

R 39 55 71 81 89 98

pH 6.8

T 30 42 61 75 83 89

R 37 49 69 80 87 97

f2 (pH 1.2) = 64.22; f2 (pH 4.5) = 61.09; f2 (pH 6.8) = 59.52.

Fig. 1. Dissolution profiles in Buffer pH 1.2.

Pink line - Lovex, blue line - Viagra.

Fig. 2. Dissolution profiles in Buffer pH 6.8


Fig. 3. Dissolution profiles in Buffer pH 4.5

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

10 15 20 25 30 45

% D

isso

luti

on

rate

Time, min

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

10 15 20 25 30 45

% D

isso

luti

on

rate

Time, min


Results of the in vitro dissolution study illustrated in Table 1 that Lovex shows dissolution profiles

similar to commercial product in 3 different buffers, with f2 values of 64.22, 61.09 and 59.52 in buffers

with pH 1.2, pH 4.5 and pH 6.8, respectively. Dissolution profiles illustrated in Fig. 1-3 shows

similarity between test (Lovex) and reference (Viagra) products.

Conclusion

About 75% of Sildenafil citrate was released in 25 min for and. The pilot batch of Lovex

showed hydration ratio of 4.1 indicating the rapid water uptake and hence faster drug release. Good

elasticity can be assured from the folding endurance. The release of both products is in required limits

for immediate release products.

According to test results, the reference and test products achieve different release profiles at

different time in three media, but these discrepancies dont influence the absorption profile and

bioavailability with consequences on the clinical use as shown by the in vivo results.

References

1. USP 30/NF 25

2. Bird, A.E. (1994) Analytical Profiles of Drug Substances and Excipients 23: 1-52.

3. A. H. Elshafeey, E. R. Bendasand O. H. Mohamed, Intranasal microemulsion of sildenafil citrate:

in vitro evaluation and in vivo pharmacokinetic study in rabbits, AAPSPharmSciTech. 10 (2009)

361367; DOI: 10.1208/s12249-009-9213-6.

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

10 15 20 25 30 45

%Dis

solu

tion

rate

Time, min

4. World Health Organization (WHO) Proposal to waive in vivo bioequivalence requirements for the

WHO model list of essential medicines immediate release, solid oral dosage forms. Working

document QAS/04.109/Rev.1.

5. J. W. Moore and H. H. Flanner, Mathematical comparison of dissolution profiles, Pharmaceutical

Technology, 20 (1996) 6474.

6. Declaration of Helsinki. As amended by the 59th World Medical Assembly (WMA). World

Medical Association, Seoul, South Korea, October 2008. Available at:

http://www.wma.net/e/ethicsunit/helsinki.htm.

, 100

.

,

1)

2)

1) , , . 2) .

2.2.29.

2.3.1.

600.0 5 %

18 20 - 5 %, 2 20 - 10 %

2.9.5.

15 2.9.1.

0.1 % 2.9.7.

75 % 45 2.9.3.

: -

-

1.0 %

2.0 %

2.2.29.

I, . 1, 5.1.4 3 1 1000 100 (). 1 Escherichia coli.

5.1.4.

90.0 % 110 % , 2.2.29.

.

I, . 1,

.

( 2.2.29.).

,

,

. ,

.

2.3.1.

20 , 0.5 10 ,

. 1 3 200 /

. , .

( 2.9.5.)

600 5 %

18 20 - 5 %, 2

20 - 10 %.

( 2.9.1.)

15 .

( 2.9.7.)

, 0.6 .

. .

(100 ) , .

. ,

, .

, .

1.0 %.

. 2.9.3,

. - 0.1 ,

- 500 , - (37.0 0.5) ,

- 100 /, - 45 .

6 .

1 .

45 25 ,

( 0.45 ) , 5

.

5 50 ,

( ).

.

14 () 10

, 5 0.1 HCl,

. 1 50 ,

0.1 HCl. ,

.

( 2.2.25).

290 10 ,

.

(), , ,

:

D1 m0 500 50 P100 0.7129 D1 m0 P 1.4258

= --------------- -------------------------------------- = ---------------------------- D0 a 50 50 5 100 D0 a

D0 ;

D1 ;

m0 , ;

a , , ;

P , ;

0.7129 .

, 45

75 % , .

. (

2.2.29) , .

300 20 100

, 70 , ,

, . 5

10 .

( ()).

1.0 () 100 ,

( ()).

():

1. , ()

,

() (1.0 %).

2. , ()

,

() (2.0 %).

:

r1 100

-------------------- ------ = , % rt

r1 ();

rt ();

.

2.6.12 , 2.6.13.

, 5.1.4, 3.

1 1000 100

().

1 Escherichia coli.

.

( 2.2.29).

510 20 100

, 10 - P (9:1 /)

10 , ,

10 ,

30 . 8000

/ 5 ( ).

(): 0.1

100 70 .

.

3.0: 7 1000

, 900 . 3.0

. .

15

-, 5

, :

- 150 4.0 5 (Symmetry Shield RP 8

);

- - 1.0 /;

- 290 ;

- 10 ;

- pH 3.0

(58:25:7)

() , :

S1m0100P1000 S1m0 P10

(/)=----- --- ----------------- b = -------------------- b, S0 m1100 100 S0 m1

S1 - , ;

S0 - , ;

m0 - , ;

m1 , ;

b - , ;

P , .

(C22H30N6O4S) 90 % 110

, .

100 . 4 (). 1

.

.

, ,

, , , , ,

.

- , ,

, , , ,

, , , , .

, 25.

.

2 .

, .

-

.

Brand name

LOVEX

Generic Name

Sildenafil

Pharmaceutical Form

Tablets

Composition

Each tablet contains:

Sildenafil (as citrate) 100 mg;

excipients: microcrystalline cellulose, zinc citrate dihydrate, aerosol, mannitol, magnesium

stearate.

ATC Code

G04BE03

Pharmacotherapeutic Group

Drugs used in erectile dysfunction.

Pharmacological Properties

Pharmacodynamic

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5).

The physiological mechanism responsible for erection of the penis involves the release of nitric oxide

(NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme

guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP),

producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.

Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the

relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual

stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP.

Studies in vitro have shown that sildenafil is selective for PDE5.

Sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological

effects.

Pharmacokinetic

Sildenafil is rapidly absorbed. Maximum observed plasma concentrations (Cmax) are reached within 30

to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral

bioavailability is 41% (range 25-63%). When sildenafil is taken with food, the rate of absorption is

reduced. The mean steady state volume of distribution (Vd) for sildenafil is 105 l. Sildenafil and its

major circulating N-desmethyl metabolite is 96% bound to plasma proteins.

Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic

microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil.

This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and potency for PDE5

approximately 50% that of the parent drug. Plasma concentrations of this metabolite are approximately

40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal

half life of approximately (T1/2) 4 h.

The total body clearance of sildenafil is 41 l/h with a resultant terminal phase half-life of 3-5 h. After

oral administration sildenafil is excreted as metabolites predominantly in the faeces (approximately

80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered

oral dose).

In volunteers with mild (creatinine clearance 50-80 mL/min) to moderate (creatinine clearance 30-49

mL/min) renal impairment the pharmacokinetics of sildenafil were not altered after receiving a 50 mg

single oral dose. In volunteers with severe renal impairment (creatinine clearance < 30 mL/min)

sildenafil clearance was reduced.

In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh A and B) sildenafil clearance was

reduced.

Indications

Treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile

erection sufficient for satisfactory sexual performance.

Dosage and Administration

For oral use. The recommended dose is 50 mg taken as needed approximately one hour before sexual

activity. Based on efficacy and toleration, the dose may be increased to 100 mg or decreased to 25 mg.

The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once

per day.

Adverse Reactions

Nervous system disorders: headache, migraine, dizziness, insomnia, depression.

Eye disorders: visual disorders, mydriasis, conjunctivitis, eye pain, cataract, scleral redness.

Gastrointestinal disorders: dyspepsia, colitis, dry mouth, diarrhea, rectal hemorrhage.

Cardiovascular disorders: angina pectoris, AV block, tachycardia, hypotension, heart failure, cardiac

arrest, cardiomyopathy, cerebrovascular thrombosis.

Respiratory system disorders: nasal congestion, asthma, laryngitis, pharyngitis, sinusitis, dyspnea,

bronchitis, cough.

Musculoskeletal disorders: arthritis, bone pain.

Hypersensitivity reactions: urticaria, pruritus, exfoliative dermatitis.

Urinary disorders: urinary tract infection.

Hematologic disorders: anemia, leukopenia.

Other: flushing, herpes simplex.

Contraindications

Known hypersensitivity to sildenafil or any ingredient in the formulation.

Concomitant use of nitric oxide donors or nitrates.

Sildenafil is not indicated for individuals below 18 years of age.

Overdose

In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at

lower doses, but the incidence rates and severities were increased.

Treatment: In cases of overdose, standard supportive measures should be adopted as required. Renal

dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is

not eliminated in the urine.

Pregnancy and Lactation

Lovex is not indicated for use by women.

Interaction with Other Medicinal Products

Lovex metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 and 2C9.

Therefore, inhibitors of these isoenzymes (such as ketoconazole, erythromycin, cimetidine) may reduce

sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.

Single doses of antacid did not affect the bioavailability of sildenafil.

No effect on Lovex pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6

inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and

related diuretics, loop and potassium sparing diuretics, ACE inhibitors, calcium channel blockers, beta-

adrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates).

Lovex did not affect the steady state pharmacokinetics of saquinavir and ritonavir.

Lovex did not potentiate the increase in bleeding time caused by acetyl salicylic acid.

Sildenafil did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean

maximum blood alcohol levels of 80 mg/dl.

Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP)

pathway, Lovex was shown to potentiate the hypotensive effects of nitrates, and its co-administration

with nitric oxide donors or nitrates in any form is therefore contraindicated.

Special Warnings and Precautions

There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular

disease. Therefore, treatments for erectile dysfunction should not be generally used in men for whom

sexual activity is inadvisable because of their underlying cardiovascular status.

Lovex should be used with caution in patients with anatomical deformation of the penis (such as

angulation, cavernosal fibrosis or Peyronies disease), or in patients who have conditions which may

predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).

In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of

sodium nitroprusside (a nitric oxide donor).

There is no safety information on the administration of sildenafil to patients with bleeding disorders or

active peptic ulceration. Therefore sildenafil should be administered to these patients only after careful

benefit-risk assessment.

Effects on Ability to Drive and Use Machines

As dizziness and altered vision were reported in clinical trials with sildenafil, patients should be aware

of how they react to Lovex, before driving or operating machinery.

Presentation


Storage

Store in a dry place at a temperature not exceeding 25 .

Protect form light.

Keep out of reach of children.

Shelf-Life

2 years.

Do not use after the expiry date printed on the pack.

Availability

Rx only.

Manufacturer

Manufactured by PharmImpEx Ltd. for SKR Ltd

Address of Manufacturer

Georgia 0159,

Tbilisi, Chiaureli St. 2

Tel. (+995) 599443856

www.lovex.ge

(LOVEX)

(Lovex)

( )

1 :

c ( ) 100 ;

: , ,

, , .

-

G04BE03

-

.

-

5 (5).

(NO) .

,

(),

.

, NO . NO

/, , 5

.

5 in vitro.

.

. (Cmax)

30-120 ( 60 ).

41% ( 25-63%).

.

105 . N-

96% .

, ,

CYP3A4 ( ) CYP2C9 ( ).

N- .

,

5 50% .

40% . N-

; (T1/2)

4 .

41 /, T1/2 - 3-5 .

, , ( 80%

) - ( 13% ).

( 50-80 /) (

30-49 /)

50 . ( 30

/ ) .

( -)

.

,

, .

.

50 1 .

100 25 .

100 . 1 /.

: , , , , .

: , , , ,

, .

: , , , ,

.

- : , ,

, , , ,

, .

: , , , ,

, , , .

- : , .

: , , .

: .

: , .

: , .

;

, ;

18 .

800

, .

: .

, ..

.

.

CYP3A4 CYP2C9,

( , , )

, .

.

CYP29 ( , ),

CYP2D6 ( ,

), ,

, , -,

CYP450 ( , )

.

.

.

80 /.

/

.

.

,

- .

(, , ),

(- ,

, ).

in vitro ,

.

, .

,

.

100 . 4 (). 1

.

, 25.

.

2 .

, .

.

SKR

0159,

, . 2

1

LOVEX

Comprims 100 mg

Mode d'emploi

Veuillez lire attentivement les instructions avec utilisation!

Conservez ces instructions car vous serez peut-tre amens les lire nouveau. Si vous avez quelques questions, veuillez consulter

votre mdecin. Ceci est votre mdicament. Ne le recommandez personne d'autre, il peut nuire la sant.

No. d'enregistrement R.2004.352.8323

Groupe pharmaco-thrapeutique et code ATC: Aphrodisiaque (mdicament pour disfonctionnement rectile) G04BE

INN: Citrate de Sildnafil

Composition: Le Citrate de Sildnafil, de la cellulose microcristalline, le zinc dihydrate de citrate, d'un arosol, le mannitol, le

starate de magnsium.

Description: Lovex est prsent en comprim blanc, gris-blanc, ou blanc-jaune, surface plate, avec des divisions diamtrales sur une

face et des marges bien structures.

INDICATIONS THERAPEUTIQUES

Lovex est prescrit pour les disfonctionnements rectiles, y compris pour les patients atteints de diabte, de surpoids, ayant subit une

prostatectomie ou un traumatisme de l'pine dorsale. Une stimulation sexuelle est ncessaire afin de rendre Lovex efficace.

CONTRE-INDICATION

Lovex est contre-indiqu pour les patients allergiques l'un des composants du comprim. Lovex est contre-indiqu pour les patients

utilisant des nitrates organiques de faon rgulire et/ou par intermittence, sous toute forme. Aucune donne clinique contrle

concernant la scurit ou l'efficacit du citrate de sildnafil n'a t effectue concernant les groupes suivants: les patients ayant une

tension artrielle basse, les patients atteints d'une rtinite pigmentaire, les patients souffrant d'infarctus du myocarde, attaque, ou

arythmie dans les six derniers mois, affaiblissment hpatique, maladie hrditaire dgnrative.

POSOLOGIE ET ADMINISTRATION

Lovex se prend par voie orale. La dose recommande est de 50mg, pris une heure avant les rapports sexuels. Selon l'efficacit du

traitement et de la tolrance, la dose peut tre augmente 100mg ou rduite 25mg. La dose maximale recommande est 100mg. La

frquence maximale recommande est d'une fois par jour. A partir d'un certain ge, la dose initiale recommande est de 25 mg. Selon

l'efficacit du traitement et de la tolrance, la dose peut tre augmente 50mg ou 100mg. Pour les patients avec des insuffisances

rnales ou hpatiques, la dose initiale recommande est de 25mg. Selon l'efficacit du traitement et de la tolrance, la dose peut tre

augmente 50mg ou 100mg. Lovex est contre-indiqu aux personnes en dessous de l'ge de 18 ans.

EFFETS SECONDAIRES

Les plus frquents sont: des maux de tte, des rougissements, des dyspepsies, des congestions nasales, des infections du systme

urinaire, des troubles de la vision, de la diarrhe, des vertiges, des ruptions cutanes.

PRECAUTIONS

Il existe un potentiel de risque cardiaque de l'activit sexuel chez les patients ayant des maladies cardiovasculaires prexistantes.

Avant de prescrire le citrate de sildnafil, le pharmacien devra prvenir avec attention les patients dj soumis une multiple

mdication contre l'hypertension. Le citrate de sildnafil possde des proprits systmiques de dilatation des veines rsultant d'une

baisse provisoire de la tension artrielle. De cette faon, Lovex augmente les effets d'hypotension dus aux nitrates organiques.

2

Le citrate de sildnafil doit tre utilis avec prcaution dans le cas de patients avec des dformations anatomiques du pnis (tels que

angulation, fibroses caverneuses ou maladie de la Peyronie) ou dans le cas d'un patient prdispos un priapisme (tels que l'anmie,

des mylomes multiples ou une leucmie).

La scurit du citrate de sildnafil est connue chez les patients souffrant d'hmorragies et chez les patients ayant une ulcration

peptique active. Avant de prescrire le citrate de sildnafil, de tels patients, une valuation des risques et de l'efficacit doit tre

effectue.

EFFETS SUR L'APTITUDE A EFFECTUER LES TACHES QUOTIDIENNES

Prendre en considration le fait que durant les tudes cliniques certains cas de maladies et de troubles de la vision ont t rapports. Il

est recommand aux patients de faire attention aux diffrentes ractions lors de leurs tches quotidiennes.

INTERACTIONS

Si vous tes sous traitement d'un autre mdicament, veuillez en rfrer votre pharmacien.

EMBALLAGE

Des comprims de 70mg N.4 sous emballage

STOCKAGE

Un endroit sec, non-expos la lumire, une temprature infrieure 25 degrs C

VALIDITE

2 ans

STATUT

Uniquement sous prescription

FABRICANT

Gorgie 0159,

Tbilissi, Chiaureli 2

Tel. (+995) 599443856

www.lovex.md

Nous vous prions de prsenter toute rclamation avec la mention du numro de srie indiqu sur la bote ou l'tiquette

110

2024,002,8000 :

( ):

etartic lifanedlis:

,lotinnam ,losorea ,etardyhid etartic cniz ,esolullec enillatsyrcorcim :

.etaraets muisengam

:

, , ,

, .

.

.

.

:) etartic lifanedlis (

, , ,

, , 6 ,

.

()

00

. 00 000,

00 . 000

. 000 00 ,

00

. 000 00

. 40

: ,, , , ,,,,

.

) , ,, , , kcolb va ( ,

, , , , , ,

, , , , , , ,

), , , , , ,, (), (

, , , , ,, ,

, , , , , ,, ,

, , . ,,

.

,

.) etartic lifanedlis(

) , etartic lifanedlis (

.

( ,,

) , ( , ,

)

, ) etartic lifanedlis (

.

.

.

. 8 00

.

.

0

2000

80000800202 22303800202

loveqsi

(Lovex)

samkurnalo saSualebis dasaxeleba

loveqsi (Lovex)

generikuli (saerTaSoriso arapatentirebuli) dasaxeleba

sildenafili

samkurnalo forma

tabletebi

Semadgenloba

1 tableti Seicavs:

sildenafils (citratis saxiT) 100 mg-s;

damxmare nivTierebebi: mikrokristaluri celuloza, TuTiis citratis dihidrati, aerosili, manitoli,

magniumis stearati.

aTq-kodi

G04BE03

klinikur-farmakologiuri jgufi

ereqtiuli disfunqciis samkurnalo saSualeba

farmakologiuri Tvisebebi

farmakodinamika. sildenafili aris cgmf-specifikuri me-5 tipis fosfodiesTerazas (fde 5) Zlieri

seleqtiuri inhibitori.

ereqciis fiziologiuri meqanizmis realizacia dakavSirebulia seqsualuri stimulaciis dros

mRvimovan sxeulSi azotis oqsidis (NO) gamoTavisuflebasTan. azotis oqsidi aaqtivebs

gianilatciklazas, rac iwvevs

cgmf-is donis momatebas, mRvimovani sxeulis gluvkunTovani qsovilis modunebas da masSi sisxlis

midinebis gazrdas.

sildenafili uSualod mRvimovani sxeulis gluv kunTebze ar moqmedebs, magram fde 5-s

blokadisa da cgmf-is stabilizaciis gziT igi aZlierebs azotis oqsidis momadunebel efeqts.

in vitro kvlevebma aCvena, rom sildenafili seleqtiurad moqmedebs fde 5-ze. sildenafilis

efeqturobis aucilebeli pirobaa seqsualuri stimulacia.

farmakokinetika. sildenafili kargad Seiwoveba kuW-nawlavis traqtidan. uzmoze peroraluri

miRebis Semdeg maqsimaluri koncentracia plazmaSi (Cmax) 30_120 wT-Si (saSualod 60 wT-Si)

miiRweva. saSualo absoluturi bioSeRwevadobaa 41% (25_63%). Wamis dros preparatis miRebisas

Sewovis siCqare mcirdeba. ganawilebis moculobaa 105 l. sildenafili da misi ZiriTadi N-demeTilis

metaboliti 96% ukavSirdebian plazmis cilebs.

sildenafili ZiriTadad RviZlSi metabolizdeba, CYP3A4 (ZiriTadi gza) da CYP2C9

(meorexarisxovani gza) izofermentebis monawileobiT. ZiriTadi metaboliti warmoiqmneba sildenafilis

N-demeTilirebis Sedegad. es metaboliti seleqtiurad moqmedebs fde 5-ze, magram misi aqtiuroba

sildenafilis aqtiurobis 50%-s Seadgens. am metabolitis koncentracia plazmaSi sildenafilis koncentraciis

40%-s Seadgens. N-demeTilis metaboliti ganicdis Semdgom metabolizms. misi naxevargamoyofis

periodi (T1/2) aris 4 sT.

sildenafilis saerTo klirensia 41 l/sT, naxevarganoyofis periodi _ 3_5 sT. igi gamoiyofa

metabolitebis saxiT, ZiriTadad nawlavebiT (miRebuli dozis daaxloebiT 80%) da naklebad _ SardiT

(daaxloebiT 13%).

Tirkmlis funqciis msubuqi da zomiri ukmarisobis mqone pirebSi sildenafilis farmakokinetika ar

icvleba. Tirkmlis funqciis mZime ukmarisobis dros klirensi Semcirebulia.

RviZlis cirozis mqone pirebSi sildenafilis klirensi mcirdema.

Cvenebebi

ereqciis darRveva, romelic ganisazRvreba sasqeso aqtis gansaxorcieleblad ereqciis miRwevisa da

SenarCunebis SeuZleblobiT.

miRebis wesi da dozebi

preparati miiReba peroralurad, sasqeso aqtamde 1 sT-iT adre. rekomendebuli erTjeradi dozaa 50

mg. efeqturobisa da amtanobis gaTvaliswinebiT SesaZlebelia dozis 100 mg-mde gazrda an 25 mg-mde

Semcireba. maqsimaluri sadReRamiso dozaa 100 mg.

preparati miiReba erTxel dReSi.

gverdiTi movlenebi

nervuli sistemis mxriv: Tavis tkivili, Sakiki, Tavbruxveva, uZiloba, depresia.

mxedvelobis mxriv: mxedvelobis darRveva, midriazi, koniunqtiviti, Tvalis tkivili, kataraqta,

sklerebis siwiTle.

saWmlis momnelebeli sistemis mxriv: dispepsia, koliti, qserostomia, diarea, reqtaluri sisxldena.

gul-sisxlZarRvTa sistemis mxriv: stenokardia, atrio-ventrikuluri blokada, taqikardia, hipotenzia,

gulis ukmarisoba, gulis gaCereba, kardiomiopaTia, Tavis tvinis sisxlZarRvebis Trombozi.

sasunTqi sistemis mxriv: asTma, laringiti, faringiti, sinusiti, qoSini, bronqiti, xvela, cxviris

lorwovani garsis SeSupeba.

sayrden-mamoZravebeli sistemis mxriv: arTritebi, Zvlebis tkivili.

alergiuli reaqciebi: WinWris cieba, qavili, eqsfoliaciuri dermatiti,

Sard-sasqeso sistemis mxriv: saSarde gzebis infeqciebi.

sisxlmbadi organoebis mriv: anemia, leikopenia.

sxva: saxis kanis hiperemia, martivi herpesi.

ukuCvenebebi

momatebuli mgrZnobeloba sildenafilis an preparatis romelime komponentis mimarT.

azotis oqsidis donatorebis an nitratebis erTdrouli miReba.

preparati ar iniSneba 18 wlamde asakis pirebSi.

Warbi dozireba

erT miRebaze 800 mg preparatis gamoyenebisas aRiniSneba gverdiTi efeqtebis gaZliereba.

mkurnaloba: simtomuri Terapia. dializi araefeqturia.

orsuloba da laqtacia

qalebSi preparati ar gamoiyeneba.

urTierTqmedeba sxva samkurnalo saSualebebTan

loveqsi metabolizdeba CYP3A4 da CYP2C9 izofermentebis monawileobiT, ris gamoc am

izofermentebis inhibitorebi (mag., CYP3A4 izofermentebis inhibitorebi ketokonazoli, eriTromicini,

cimetidini) amcireben, xolo induqtorebi _ zrdian sildenafilis klirens.

antacidebis erTjeradi miReba ar moqmedebs sildenafilis bioSeRwevadobaze.

CYP2C9 izofermentebis inhibitorebi (mag., tolbutamidi, varfarini), CYP2D6 inhibitorebi (mag.,

serotoninis ukuSTanqvis seleqciuri blokatorebi, tricikluri antidepresantebi), Tiaziduri da Tiazidis

msgavsi diurezuli saSualebebi, maryuJovani da kaliumis Semnaxveli diurezuli saSualebebi, agf

inhibitorebi, kalciumis arxebis blokatorebi, -adrenoreceptorebis antagonistebi, CYP450 metabolizmis

induqtorebi (rifampicini, barbituratebi) ar moqmedeben loveqsis farmakokinetikaze.

loveqsi ar moqmedebs ritonavirisa da sakvinaviris farmakokinetikaze.

loveqsi damatebiT ar axangrZlivebs sisxldenis dros acetilsalicilis mJavas miRebisas.

sildenafili ar aZlierebs alkoholis hipotenziur moqmedebas janmrTel pirebSi, Tu alkoholis

maqsimaluri koncentracia sisxlSi Seadgens 80 mg/dl-s.

NO/cgmf-is cvlis procesze moqmedebis gamo loveqsi zrdis nitratebis hipotenzur efeqts. loveqsisa

da nitratebis an NO-s sxva donorebis erTdrouli gamoyeneba ukunaCvenebia.

gansakuTrebuli miTiTebebi

seqsualuri aqtivobiT ganpirobebuli gul-sisxlZarRvTa sistemis mxriv garkveuli uaryofiTi

efeqtebis ganviTarebis garkveuli riskis gamo, preparatis daniSvnamde saWiroa pacientis saTanado

gamokvleva.

preparati sifrTxiliT gamoiyeneba sasqeso organos anatomiuri defeqtis dros (mag., angulacia,

kavernozuli fibrozi an peironis daavadeba) an iseTi daavadebebis dros, romlebmac SeiZleba priapizmis

ganviTareba gamoiwvios (namgliseburi anemia, mravlobiTi mieloma, leikozi).

trombocitebze Catarebulma in vitro kvlevebma aCvena, rom sildenafili aZlierebs natriumis

nitroprusidis antiagregantul Tvisebebs.

informacia preparatis gamoyenebis usafrTxoebis Sesaxeb kuWisa da Tormetgoja nawlavis

peptikuri wylulis mqone pacientebSi, aseve sisxldeniT mimdinare daavadebebis dros ar moipovba, ris

gamoc aseT pacientebSi preparati iniSneba mxolod riskisa da sargebelis Sefasebis Semdeg.

preparatis zemoqmedeba avtotransportisa da meqanizmebis marTvis unarze: loveqsis klinikuri

kvlevebis dros aRiniSneboda Tavbruxveva da mxedvelobis darRveva, ris gamoc satransporto

saSualebebis marTvis an potenciurad saSiSi meqanizmebis gamoyenebis dros saWiroa ganisazRvros

preparatis miRebaze pacientis individualuri reaqcia.

SefuTva

100 mg tabletebi. 4 tableti konturul ujredovan SefuTvaSi (blisteri), 1 blisteri muyaos kolofSi.

Senaxvis pirobebi

inaxeba mSral, sinaTlisagan dacul adgilas, ara umetes 25C temperaturaze.

inaxeba bavSvebisaTvis miuwvdomel adgilas.

vargisobis vada

2 weli.

SefuTvaze aRniSnuli vadis gasvlis Semdeg preparatis gamoyeneba dauSvebelia.

gacemis wesi

gaicema receptiT.

mwarmoebeli

Sps `farmimpeqsi~ Sps `SKR~-is dakveTiT

mwarmoeblis misamarTi

saqarTvelo 0159,

Tbilisi, Wiaurelis q. #2

Documents

lovex registr (2)