How does it work?

Coversyl arginine plus tablets contain two active ingredients,perindopril and indapamide. Perindopril is a type of medicine called an ACEinhibitor. Indapamide is a type of medicine called a diuretic. These are bothmedicines used to lower high blood pressure.

ACE inhibitors such as perindopril work by blocking the actionof a compound in the body called angiotensin converting enzyme (ACE). NormallyACE produces another compound called angiotensin II, as part of the body'snatural control of blood pressure. Angiotensin II causes blood vessels toconstrict and narrow, which increases the pressure within the blood vessels.

As perindopril blocks the action of ACE, it reduces theproduction of angiotensin II. This means that the blood vessels are allowed torelax and widen. The overall effect of this is a drop in blood pressure, henceperindopril can be used to lower high blood pressure.

Diuretics such as indapamide are sometimes referred to as ‘watertablets’. They remove excess fluid from the body by increasing the productionof urine.

Diuretics act in the kidneys. They work by causing the kidneysto increase the amount of salts, such as potassium and sodium, that arefiltered out of the blood and into the urine. When these salts are filtered outof the blood by the kidneys, they draw water alongside them. As diureticsincrease the removal of salts from the blood, they also cause more water to bedrawn out of the blood and into the urine.

Removing water from the blood decreases the volume of fluidcirculating through the blood vessels. This subsequently decreases the pressurewithin the blood vessels. Diuretics can therefore be used to lower high bloodpressure.

The combination of perindopril with indapamide is used whenblood pressure has not been lowered sufficiently using perindopril on its own.

What is it used for?

• High blood pressure with no known cause (essential hypertension).

Warning!

• Coversyl arginine plus tablets replaced Coversyl plus tablets in April 2008. Coversyl arginine plus tablets contain a different salt of perindopril to the old Coversyl plus tablets (perindopril arginine instead of perindopril tert-butylamine). This new salt has an extended shelf-life and greater stability. Coversyl arginine plus is equivalent to the old Coversyl plus in terms of safety and effectiveness, and the action of the medicine has not changed. However, the new tablets come in different packaging and in a different strength to the old Coversyl plus tablets. Coversyl arginine plus tablets contain 5mg perindopril arginine, which is equivalent to the 4mg perindopril tert-butylamine in the old Coversyl plus tablets. If you have any questions or concerns abou this change you should talk to your pharmacist.
• Diuretics cause your kidneys to produce more urine, so this medicine should preferably be taken in the morning before breakfast, rather than before going to bed. This will avoid disturbing your sleep with the need to get up in the night to visit the toilet. Seek further advice from your doctor or pharmacist.
• This medicine may make you feel dizzy as a result of the drop in your blood pressure. If you feel dizzy this can usually be relieved by lying down until the symptoms pass. If affected you should avoid performing potentially hazardous tasks such as driving or operating machinary. If you frequently feel dizzy you should let your doctor know, as your dose of this medicine may need reducing.
• Alcohol may enhance the blood pressure lowering effect of this medicine, which can increase dizziness and may increase the risk of fainting.
• ACE inhibitors can sometimes cause an allergic reaction called angioedema. Stop taking this medicine and consult your doctor immediately if you experience difficulty breathing or swallowing, or swelling of your face, lips, tongue, throat, hands, feet or ankles while taking this medicine. This type of allergic reaction has been reported more frequently in people of Afro-Caribbean origin.
• Your blood pressure, kidney function and the levels of electrolytes such as potassium, sodium and calcium in your blood should be regularly monitored while you are taking this medicine.
• If you need a test to assess the functioning of your parathyroid gland, your doctor may ask you to stop taking this medicine beforehand, as it may interfere with the test results.

Use with caution in

• Elderly people.
• Decreased liver function.
• Liver cirrhosis.
• Decreased kidney function.
• Narrowing of the artery which supplies blood to the kidneys (renal artery stenosis).
• High blood pressure caused by compression or blockage of the arteries that carry blood to the kidneys (renovascular hypertension).
• Heart failure.
• People with low fluid volume or salt levels in the body, eg due to diuretic therapy, low-sodium diet, dehydration, diarrhoea or vomiting.
• People taking other medicines for high blood pressure, particularly diuretics (see end of factsheet).
• People with hardening of the arteries (athersclerosis) in the heart (cardiovascular disease), brain (cerebrovascular disease) or legs (peripheral vascular disease).
• Narrowing of the main artery of the body (aortic stenosis).
• Heart disease characterised by thickening of the internal heart muscle (hypertrophic cardiomyopathy).
• People with an abnormal heart beat seen on a heart monitoring trace (ECG) as a 'prolonged QT interval'.
• Diseases affecting connective tissue, eg scleroderma, systemic lupus erythematosus or rheumatoid arthritis (collagen vascular diseases).
• Diabetes.
• History of gout.
• People undergoing therapy to decrease allergy to bee or wasp stings (desensitisation).
• People receiving therapy to remove certain types of fat from the blood using a machine (LDL apheresis).

Not to be used in

• Allergy to other ACE inhibitor medicines.
• Allergy to medicines from the sulphonamide group, eg the antibiotic sulfamethoxazole.
• History of swelling of the lips, face or tongue (angioedema) with no known cause, or caused by previous use of an ACE inhibitor medicine.
• Hereditary angioedema (angioneurotic oedema).
• Severely decreased kidney function.
• People having kidney dialysis.
• Severely decreased liver function.
• Impairment of brain function caused by liver disease (hepatic encephalopathy).
• Uncontrolled heart failure.
• Low blood potassium levels (hypokalaemia).
• Pregnancy.
• Breastfeeding.
• Children.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (Coversyl arginine plus tablets contain lactose).

This medicine should not be used if you are allergic to one orany of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such anallergy.If you feel you haveexperienced an allergic reaction, stop using this medicine and inform yourdoctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy orbreastfeeding. However, other medicines may be safely used in pregnancy orbreastfeeding providing the benefits to the mother outweigh the risks to theunborn baby. Always inform your doctor if you are pregnant or planning apregnancy, before using any medicine.

• This medicine must not be used during pregnancy, particularly during the second and third trimesters, as it may be harmful to the unborn baby. Seek further medical advice from your doctor. If you get pregnant while taking this medicine, stop taking it and consult your doctor immediately.
• This medicine passes into breast milk. The manufacturer states that it should not be taken by women who are breastfeeding. Seek further medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Just because a side effect is statedhere does not mean that all people using this medicine will experience thator any side effect.

Common (affect between 1 in 10 and 1 in 100 people)

• Dry cough.
• Disturbances of the gut such as constipation, nausea or abdominal pain.
• Dry mouth.
• Alteration in taste.
• Loss of appetite.
• Low blood potassium level (hypokalaemia).

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Feeling of weakness.
• Headache.
• Low blood pressure (hypotension).
• Dizziness.
• Pins and needles sensations.
• Sleep disturbances.
• Changes in mood.
• Skin rashes.
• Muscle cramps.
• Problems with kidney function.

Very rare (affect less than 1 in 10,000 people)

• Severe swelling of lips, face, tongue or throat (angioedema - see warning above).
• Disturbances in the normal levels of blood cells in the blood (tell you doctor if you get a sore throat, mouth ulcers, high temperature (fever), or feel tired or generally unwell while taking this medicine).
• Inflammation of the pancreas (pancreatitis).
• Problems with liver function, including jaundice or hepatitis (consult your doctor promptly if you develop unexplained itching, yellowing of the skin or eyes, unusually dark urine, nausea and vomiting, abdominal pains, loss of appetite or flu-like symptoms while taking this medicine).

The side effects listed above may not include all of the sideeffects reported by the medicine'smanufacturer.For moreinformation about any other possible risks associated with this medicine,please read the information provided with the medicine or consult your doctoror pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines whiletaking this one, to ensure that thecombination is safe.

This medicine will have an additive effect with other medicinesthat decrease blood pressure, particularly other medicines used to treat highblood pressure (antihypertensives). In people taking antihypertensive medicinesit may cause a large drop in blood pressure with the first dose or after anydose increases, particularly in people taking diuretic medicines such asfurosemide. This may cause dizziness, which can usually be relieved by lyingdown until the symptoms pass. If you frequently feel dizzy while taking thismedicine in combination with other blood pressure lowering medicines you shouldlet your doctor know, as your doses may need adjusting. Other medicines thatdecrease blood pressure include the following:

• other ACE inhibitors, eg captopril
• aldesleukin
• alpha-blockers such as prazosin
• alprostadil
• angiotensin II receptor antagonists such as losartan
• antipsychotics
• benzodiazepines, eg temazepam, diazepam
• baclofen
• beta-blockers such as propranolol
• calcium-channel blockers such as verapamil, nifedipine
• clonidine
• diazoxide
• diuretics, eg furosemide, bendroflumethiazide
• dopamine agonists, eg bromocriptine, apomorphine
• hydralazine
• levodopa
• MAOI antidepressants, eg phenelzine
• methyldopa
• minoxidil
• moxonidine
• moxisylyte
• nicorandil
• nitrates, eg glyceryl trinitrate
• tizanidine.

Non-steroidal anti-inflammatory drugs (NSAIDs, eg indometacin,aspirin, ibuprofen) may reduce the blood pressure lowering effect of thismedicine, and may increase the risk of a decline in kidney function.

There may be a risk of raised potassium levels in the blood(hyperkalaemia) if any of the following medicines are taken with perindopril,hence these are not normally recommended for use in combination with thismedicine. If you are taking any of the following with this medicine you shouldhave regular blood tests to monitor the amount of potassium in your blood:

• angiotensin II receptor antagonists, eg losartan
• ciclosporin
• drospirenone
• heparin
• potassium-containing salt substitutes (eg Lo-Salt)
• potassium salts, eg potassium citrate for cystitis
• potassium-sparing diuretics (eg spironolactone, triamterene, amiloride)
• potassium supplements.

There may be a risk that the amount of potassium in the bloodcould fall too low (hypokalaemia) if any of the following medicines are takenin combination with this medicine. If you are taking any of the following withthis medicine you should have regular blood tests to monitor the amount ofpotassium in your blood:

• amphotericin
• corticosteroids
• carbenoxolone
• beta-agonist bronchodilators such as salbutamol
• stimulant laxatives, eg bisacodyl.

If the amount of potassium in your blood drops too low and youare also taking any of the following medicines, there may be an increased riskof abnormal heart beats:

• medicines for abnormal heartbeats (antiarrhythmics), eg amiodarone, procainamide, disopyramide, sotalol
• cardiac glycoside medicines, such as digoxin
• the anthistamines astemizole or terfenadine (no longer available in the UK)
• certain antimalarials, eg halofantrine, chloroquine, quinine
• certain antipsychotics, eg thioridazine, chlorpromazine, sertindole, haloperidol
• intravenous erythromycin or pentamidine
• cisapride.

This medicine may increase the blood level of the medicinelithium and for this reason, it is not normally recommended for people takinglithium. People taking this medicine in combination with lithium should havethe level of lithium in their blood closely monitored.

Perindopril may possibly enhance the blood sugar lowering effectof insulin and oral antidiabetic medicines, and so could increase the risk oflow blood sugar (hypoglycaemia). On the other hand, indapamide may increaseblood sugar levels. People with diabetes should therefore carefully monitortheir blood sugar while taking this medicine, particularly in the first fewweeks of treatment.

There may be an increased risk of a drop in the normal numbersof blood cells in the blood if this medicine is used in combination with any ofthe following medicines:

• allopurinol
• azathioprine
• immunosuppressant therapy
• procainamide.

If you are taking any of these in combination with thismedicine, you should have regular blood tests to monitor the levels of yourblood cells, particularly if you also have any kidney problems or diseasesaffecting connective tissue, eg scleroderma, systemic lupus erythematosus(collagen vascular diseases). Tell your doctor if you experience any signs ofinfection, such as fever, sore throat or mouth ulcers, as these could be signsof problems with your white blood cells.

There may be a risk of raised blood calcium levels if thismedicine is taken with calcium supplements or calcium salts.

Other medicines containing the same active ingredients

There are currently no other medicines available in the UK thatcontain both perindopril and indapamide as the active ingredients.

Coversyl arginine containsjust perindopril.

Natrilix containsjust indapamide.