PLEASE READ THIS LEAFLET CAREFULLY BEFORE YOUSTART TO TAKE YOUR TABLETSThis medicine has been prescribed for you personnally andyou should not pass it on to others. It may harm them, evenif their symptoms are the same than yours. This leafletcontains a summary of the information on your medicine. Ifyou have questions or want more information, please askyour doctor or pharmacist. Keep this leaflet while you aretaking CoAprovel tablets, as you may want to read it again.

COMPOSITIONThe active substances in CoAprovel tablets are irbesartan andhydrochlorothiazide. Each tablet of CoAprovel 150/12.5 mgcontains 150 mg irbesartan and 12.5 mg hydrochlorothiazide.The tablets contain the following excipients: microcrystallinecellulose, croscarmellose sodium, lactose monohydrate,hypromellose, silicon dioxide, magnesium stearate, titaniumdioxide (E 171) macrogol, red and yellow ferric oxides (E 172),carbauna wax.CoAprovel film-coated tablets are supplied in blister packs of14, 28, 56 or 98. Not all pack sizes may be marketed.

TYPE OF MEDICINECoAprovel is a combination of two active substances, irbesartanand hydrochlorothiazide.Irbesartan belongs to a group of medicines known asangiotensin-II receptor antagonists. Angiotensin-II is a substanceproduced in the body that binds to receptors in blood vesselscausing them to tighten. This results in an increase in bloodpressure. Irbesartan prevents the binding of angiotensin-II tothese receptors, causing the blood vessels to relax and theblood pressure to lower.Hydrochlorothiazide is one of a group of medicines (calledthiazide diuretics) that causes increased urine output and socauses a lowering of blood pressure.The two active ingredients in CoAprovel work together tolower blood pressure further than if either was given alone.

MARKETING AUTHORISATION HOLDERSANOFI PHARMA BRISTOL-MYERS SQUIBB SNC174, avenue de France - 75013 Paris - France.

MANUFACTURERSanofi Winthrop Industrie - 1, rue de la Vierge - Ambarès etLagrave - 33565 Carbon Blanc Cedex - France.

WHEN SHOULD COAPROVEL BE USED?CoAprovel is used in the treatment of high blood pressure(hypertension), when a combination of two active substancesis deemed appropriate. This is usually the case when treatmentwith one active substance alone did not provide adequatecontrol of your blood pressure.Your doctor measured your blood pressure and found it to be

above the normal range for your age. High blood pressure, ifnot treated, can damage blood vessels in several organs suchas the heart, the kidneys, the brain and the eyes. In someinstances, this may lead to heart attacks, heart or kidneyfailure, strokes, or blindness. There are usually no symptomsof high blood pressure before damage occurs. Thus,measurement of the blood pressure is necessary to verify ifit is in the normal range or not.High blood pressure can be treated and controlled withmedicines such as CoAprovel. Your doctor may also haverecommended that you adjust your lifestyle to help to loweryour high blood pressure (losing weight, avoiding smoking,reducing alcohol consumption and restricting the amount ofsalt in the diet). Your doctor may also have encouraged thepractice of regular, mild (not strenuous) exercise such aswalking and swimming.

IMPORTANT INFORMATION BEFORE TAKING COAPROVEL:

When should CoAprovel not be used?Do not take CoAprovel if:•you are allergic to irbesartan and hydrochlorothiazide, anyother ingredients included in CoAprovel or to sulfonamide-derived medicines,

•you are in the second or third trimester of pregnancy,•you are breast-feeding,•you have severe liver or kidney problems (ask your doctor ifyou have any doubt),

•you have difficulty in producing urine,•you have a condition which is associated with persistentlyhigh calcium or low potassium levels in your blood.

Other appropriate precautions before useThere are certain conditions that you may have, or have had,which require special care before or while taking CoAprovel.Therefore, before taking this medicine, you should have toldyour doctor if you suffer from:•excessive vomiting or diarrhoea,•kidney problems, including kidney transplantation,•heart problems,• liver problems,•diabetes or• lupus erythematosus (also known as lupus or SLE).You should also tell your doctor if you are on a low-salt diet.Signs such as abnormal thirst, dry mouth, general weakness,drowsiness, muscle pain or cramps, nausea, vomiting, or anabnormally fast heart beat may indicate an excessive effectof hydrochlorothiazide (contained in CoAprovel) for which youshould consult your doctor.If you are to undergo any surgery or receive anaesthetics,you should make sure the doctor knows that you are takingCoAprovel tablets.

1

196981V3 - 15/03/2007

English/Urdu

Stéphanie GENELOT

Ambarès

170 mm x 210 mm DC

Laetus code 8139

3

Eurostile

6 points mini

Assembly Card Not DC.3 Technical Card NOT RL - DC 45 g Technical Constraints NOT. SPOT. COD. ech 1

Leaflet Co Aprovel RM 150 mg 28 tablets

Pakistan

Pantone 296 CVC, Pantone 2706 CVC, Pantone Process Magenta CVC (from 100 to 65%)

film-coated tabletsirbesartan/hydrochlorothiazide

150/12.5 mg

Hydrochlorothiazide contained in this medication couldproduce a positive result in an anti-doping test.

CAN YOU TAKE COAPROVEL WITH OTHER MEDICINES?You should have informed your doctor of any medicines youare taking or have recently taken. These include medicinesobtained without prescription.Diuretic agents such as the hydrochlorothiazide contained inCoAprovel may interact with other medicines. Preparationscontaining lithium should not be taken with CoAprovel withoutclose supervision by your doctor. Special precautionarymeasures (e.g. blood tests) may be appropriate if you takepotassium supplements, potassium-containing salt substitutesor potassium sparing medicines, other diuretics (watertablets), some laxatives, medicines for the treatment of gout,therapeutic vitamin D supplements, medicines to controlheart rhythm or for diabetes (oral agents or insulins). It isalso important for your doctor to know if you are taking othermedicines to reduce your blood pressure, steroids, medicines totreat cancer, pain killers or arthritis medicines.

CAN COAPROVEL BE USED DURING PREGNANCY ORBREAST-FEEDING?Tell your doctor before taking CoAprovel if you are pregnant,think you may be pregnant, are planning to be pregnant or ifyou are breast-feeding. It is preferable not to use CoAprovelin the first trimester of pregnancy. If you become pregnantwhile on CoAprovel treatment, refer to your doctor withoutdelay. CoAprovel should not be taken during the second orthird trimester of pregnancy, or while breast-feeding (See“When should CoAprovel not be used?”). A switch to a suitablealternative treatment should be carried out in advance of aplanned pregnancy.

CAN YOU DRIVE OR OPERATE MACHINERY WHILETAKING COAPROVEL?CoAprovel is unlikely to affect your ability to drive or use machines.However, occasionally dizziness or weariness may occurduring treatment of high blood pressure. If you experiencethese, you should consult your doctor before attempting suchactivities.

HOW SHOULD YOU TAKE COAPROVEL?The tablets should be taken regularly as directed by your doctor.CoAprovel will usually be prescribed by your doctor when yourprevious treatment for high blood pressure did not provideappropriate blood pressure reduction. Your doctor will instructyou how to switch from the previous treatment to CoAprovel.The usual dose of CoAprovel is one or two tablets a day. Themaximal blood pressure lowering effect should be reached6-8 weeks after beginning treatment. If you have theimpression that the effect of CoAprovel is too strong ortoo weak, talk to your doctor or pharmacist.CoAprovel can be taken with or without food. The tabletsshould be swallowed with a drink of water. You should try totakeyour daily dose at about the same time each day. It isimportant that you continue to take CoAprovel until yourdoctor tells you otherwise.CoAprovel should not be given to children (< 18 years).

OVERDOSEIf you accidentally take too many tablets, or a child swallowssome, contact your doctor immediately.

MISSING A DOSEIf you accidentally miss a daily dose, just take the next dose asnormal. Do not take a double dose to make up for the misseddose.

ARE THERE SIDE EFFECTS WHEN TAKING COAPROVEL?All medicines may cause some side effects.If any side effects occur, they are likely to be mild and temporary.However, some effects may be serious and require medicalattention.The most common side effects reported in clinical studiesare: nausea/vomiting, abnormal urination, fatigue, dizziness(including when getting up from a lying or sitting position). Thefollowing less common effects have also been seen: diarrhoea,low blood pressure, faintness, fast heart beat,flushing,swelling and problems with sexual performance.In addition your doctor may identify abnormal changes in yourblood components (decrease in serum potassium andsodium, increase in BUN, creatinine and creatine kinase).Occasional side effects reported since the marketing ofCoAprovel are: headache, ringing in the ears, cough, tastedisturbance, indigestion, pain in joints and muscles, liverfunction disorders and impaired renal function. As with similar medicines, rare cases of allergic skin reactions(rash, urticaria), as well as localised swelling of the face, lipsand/or tongue have been reported in patients taking irbesartan.If you think you are developing such a reaction or get short ofbreath stop taking CoAprovel and seek immediate medicalattention.As for any combination of two active substances, side effectsassociated with each individual component cannot be excluded.In patients taking irbesartan alone, in addition to the sideeffects listed above, chest pain has also been reported.The other component of CoAprovel (hydrochlorothiazide) hasbeen associated rarely with other more serious side effectsmainly affecting the blood, the skin or the kidneys. While thiswas not observed with CoAprovel, occurrence of such sideeffects cannot be excluded.It is known that side effects associated with hydrochlorothiazidemay increase with higher doses of hydrochlorothiazide.If you notice any other side effects while taking CoAprovel,you should inform your doctor or pharmacist and ask for theiradvice.

HOW SHOULD YOU STORE YOUR COAPROVEL TABLETS?Keep out of the reach and sight of children.Do not store above 30°C.Store in the original package.You will see an expiry date on the carton and on the blister.Do not use the tablets after this date.Do not remove the tablets from the blister pack until you areready to take the medicine.

DATE OF LAST REVISION OF THIS LEAFLETSeptember 2005

OTHER INFORMATIONIf you would like more information on your disease or treatment,you should ask your doctor or pharmacist.

2

196981V3 - 15/03/2007

English/Urdu

Stéphanie GENELOT

Ambarès

170 mm x 210 mm DC

Laetus code 8139

3

Eurostile

6 points mini

Assembly Card Not DC.3 Technical Card NOT RL - DC 45 g Technical Constraints NOT. SPOT. COD. ech 1

Leaflet Co Aprovel RM 150 mg 28 tablets

Pakistan

Pantone 296 CVC, Pantone 2706 CVC, Pantone Process Magenta CVC (from 100 to 65%)

3

196981V3 - 15/03/2007

English/Urdu

Stéphanie GENELOT

Ambarès

170 mm x 210 mm DC

Laetus code 8139

3

Eurostile

6 points mini

Assembly Card Not DC.3 Technical Card NOT RL - DC 45 g Technical Constraints NOT. SPOT. COD. ech 1

Leaflet Co Aprovel RM 150 mg 28 tablets

Pakistan

Pantone 296 CVC, Pantone 2706 CVC, Pantone Process Magenta CVC (from 100 to 65%)

4 196981

170x2

10m

mD

C

196981V3 - 15/03/2007

English/Urdu

Stéphanie GENELOT

Ambarès

170 mm x 210 mm DC

Laetus code 8139

3

Eurostile

6 points mini

Assembly Card Not DC.3 Technical Card NOT RL - DC 45 g Technical Constraints NOT. SPOT. COD. ech 1

Leaflet Co Aprovel RM 150 mg 28 tablets

Pakistan

Pantone 296 CVC, Pantone 2706 CVC, Pantone Process Magenta CVC (from 100 to 65%)