How does it work?

Exforge tablets contain two active ingredients, amlodipine andvalsartan. Valsartan is a type of medicine called an angiotensin II receptorantagonist. Amlodipine is a type of medicine called a calcium-channel blocker.These are both medicines used to lower high blood pressure.

Valsartan works by preventing the action of a hormone in thebody called angiotensin II. Angiotensin II normally acts on special receptorsin the body, with two main results. It causes the peripheral blood vessels tonarrow, and it also stimulates the production of another hormone calledaldosterone. Aldosterone causes salt and water to be retained by the kidneys,which increases the volume of fluid in the blood vessels.

Valsartan blocks the receptors that angiotensin II acts on andso prevents its actions. The main result of this is that the peripheral bloodvessels are allowed to widen, which means that there is more space and lessresistance in these blood vessels. This helps lower blood pressure.

Amlodipine works by slowing the movement of calcium through themuscle cells that are found in the walls of blood vessels and heart. It doesthis by blocking 'calcium channels' in these muscle cells. Calcium is needed bymuscle cells in order for them to contract, so by depriving them of calcium,amlodipine causes the muscle cells to relax. Amlodipine acts specifically onthe muscle cells in the walls of arteries, causing them to relax. This allowsthe arteries in the body to widen.

The relaxing and widening of the small arteries in the bodydecreases the resistance that the heart has to push against in order to pumpthe blood around the body. This reduces the pressure within the blood vessels.Amlodipine can therefore be used to treat high blood pressure.

What is it used for?

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

This combination of valsartan and amlodipine is used when bloodpressure has not been lowered sufficiently by taking valsartan or amlodipinealone.

How do I take it?

• One Exforge tablet should be taken once a day, preferably at the same time each day.
• The tablets can be taken either with or without food.

Warning!

• 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 machinery. If you frequently feel dizzy you should let your doctor know, as your dose of this medicine may need adjusting.
• Your blood pressure should be regularly monitored while you are taking this medicine.
• If you have any problems with your kidneys your kidney function and the amount of potassium in your blood should be regularly monitored while you are taking this medicine.

Use with caution in

• People over 65 years of age.
• Moderately decreased kidney function.
• People with narrowing of the arteries that supply blood to the kidneys (renal artery stenosis).
• People who have had a kidney transplant.
• Mild to moderately decreased liver function.
• Blockage of the bile ducts (biliary obstruction).
• Heart failure.
• People with narrowing of the main artery that leaves the heart to supply blood to the body (aortic stenosis).
• Heart valve disease (mitral valve stenosis).
• Heart disease characterised by thickening of the internal heart muscle (hypertrophic cardiomyopathy).
• People with low fluid volume or salt levels in the body, eg due to diuretic therapy, low-sodium diet, diarrhoea or vomiting.
• Hereditary blood disorders called porphyrias.

Not to be used in

• Allergy to related calcium channel blockers (dihydropyridines).
• Severely decreased liver function.
• Rare form of liver disease involving the bile ducts (biliary cirrhosis).
• Failure of the normal flow of bile from the liver to the intestines (cholestasis).
• Severely decreased kidney function or people who are having kidney dialysis.
• Angina not well controlled by medical treatment (unstable angina).
• Failure of the heart to maintain adequate circulation of blood (cardiogenic shock).
• Disorder of the adrenal glands in which there is overproduction of the hormone aldosterone (primary hyperaldosteronism).
• Children or adolescents under the age of 18 years.
• Pregnancy.
• Breastfeeding.

This medicine should not be used if you are allergic to any of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such an allergy.

If you feel you have experienced an allergic reaction, stopusing this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

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

• This medicine should not be used in pregnancy, particularly in 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.
• It is not known if valsartan and/or amlodipine pass into breast milk. This medicine should therefore not be used during breastfeeding. Mothers will need to either stop breastfeeding while taking this medicine, or not take this medicine. This will depend on how important the medicine is for treating the mother’s blood pressure. It is important to seek 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, it 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)

• Headache.
• Excessive fluid retention in the body tissues, resulting in swelling (oedema).
• Swelling of feet or ankles (peripheral oedema).
• Fatigue.
• Flushing.
• Cold and flu like symptoms.
• Inflammation of the nose and throat, causing a blocked or runny nose and sore throat (nasopharyngitis).
• Weakness or loss of strength (asthenia).
• Hot flushes.

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

• Dizziness.
• Sleepiness.
• Pins and needles (paraesthesia).
• A drop in blood pressure that occurs when going from lying down to sitting or standing, which results in dizziness and lightheadedness (postural hypotension).
• Sensation of spinning (vertigo).
• Increased heart rate (tachycardia).
• Awareness of your heart beat (palpitations).
• Cough.
• Pain in the muscles or joints.
• Skin reactions such as redness, rash.
• Disturbances of the gut such as nausea, vomiting, indigestion, diarrhoea, constipation, abdominal pain.
• Dry mouth.

Rare (affect between 1 in 1000 and 1 in 10,000 people)

• Increased urinary frequency.
• Impotence
• Anxiety.
• Sensation of ringing, or other noise in the ears (tinnitus).
• Visual disturbances.
• Sensation of heaviness.
• Excessive sweating.
• Muscle spasms.
• Low blood pressure.
• Fainting.
• Itchy skin.

The side effects listed above may not include all of the sideeffects reported by the medicine's manufacturer.

For more information about any other possible risks associatedwith this medicine, please read the information provided with the medicine orconsult your doctor or 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 make sure that thecombination is safe.

This medicine is likely to have an additive effect with other medicines that decrease blood pressure, particularly medicines that are used to treat high blood pressure (antihypertensives). This may cause dizziness, which can usually be relieved by lying down until the symptoms pass. If you feel dizzy while taking this medicine in combination with other medicines that can lower blood pressure you should let your doctor know, as your doses may need adjusting. Other medicines that decrease blood pressure include the following:

• ACE inhibitors, eg enalapril
• aldesleukin
• alpha-blockers such as prazosin
• alprostadil
• other angiotensin II receptor antagonists such as losartan
• antipsychotics such as chlorpromazine
• benzodiazepines, eg temazepam, diazepam
• baclofen
• beta-blockers such as propranolol
• other 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
• sildenafil
• tizanidine.

Valsartan may increase the level of potassium in your blood. Ifthis medicine is taken with other medicines that can increase blood potassiumlevels, this effect may be enhanced. Such medicines include those listed below. If any of these are used in combination with Exforge, the amount ofpotassium in your blood should be monitored:

• ciclosporin
• drospirenone
• heparin
• non-steroidal anti-inflammatory drugs, eg indometacin, diclofenac, ibuprofen
• potassium-sparing diuretics (eg spironolactone, triamterene, amiloride)
• potassium salts, eg potassium citrate for cystitis
• potassium supplements
• potassium-containing salt substitutes such as Lo-Salt
• tacrolimus
• trimethoprim.

Valsartan may increase blood levels of themedicine lithium, and this medicine is therefore not recommended for peopletaking lithium. If it is necessary to take both, your doctor should carefullymonitor your blood levels of lithium and you should let your doctor know if youexperience any signs that your lithium level is increasing, for example, lossof appetite, diarrhoea, vomiting, blurred vision, muscle weakness, lack ofco-ordination, drowsiness, tremor, unsteadiness, muscle twitching, ringing inthe ears or confusion.

Amlodipine increases the blood level of the cholesterol-lowering medicine simvastatin and this could increase the chance of simvastatin having side effects on your muscles. Your dose of simvastatin should not be higher than 40mg daily if you are also taking Exforge.

The following medicines may increase the amount of amlodipine inyour blood and this could increase the risk of its side effects:

• clarithromycin
• diltiazem
• erythromycin
• itraconazole
• ketoconazole
• protease inhibitors for HIV infection, eg ritonavir, nelfinavir, saquinavir
• telithromycin
• verapamil.

If you take any of these with Exforge, you should tell your doctor if you feel dizzy or experience any other side effects, as the dose of your Exforge may need to be reduced.

The following medicines may decrease the amount of amlodipine inyour blood and so could make it less effective. As a result, your doctor mayneed to prescribe you a higher dose of Exforge tablets if you aretaking any of these:

• carbamazepine
• phenytoin
• phenobarbital
• rifampicin
• the herbal remedy St. John's wort (hypericum perforatum).

The following medicines may reduce the blood pressure lowering effect of this medicine:

• corticosteroids, such as dexamethasone or prednisolone
• oestrogens, such as those in the contraceptive pill
• regular use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, diclofenac or indomethacin (occasional painkilling doses are unlikely to have a significant effect).

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK thatcontain both valsartan and amlodipine.

Diovan containsjust valsartan.

Istin containsjust amlodipine. Amlodipine tablets are also available as the generic medicine,ie without a brand name.