How does it work?

Tarka capsules contain two active ingredients, trandolapril and verapamil. Trandolapril is a type of medicine called an ACE inhibitor and verapamil is a type of medicine called a calcium channel blocker. These are both medicines used to lower high blood pressure. They work in different ways to lower high blood pressure.

Verapamil works by slowing down the movement of calcium through muscle cells that are found in the heart and the walls of blood vessels. It does this by blocking 'calcium channels' on these muscle cells. Calcium is needed by the muscle cells in order for them to contract. By depriving them of calcium, verapamil causes the muscle cells to relax. This action of verapamil has two main effects; it slows down the rate at which the heart beats and it allows the blood vessels in the body to widen.

When the heart beats more slowly, the pressure at which the blood is pumped out of the heart is reduced. When the blood vessels in the body relax and widen, this decreases the resistance that the heart has to push against in order to pump the blood around the body. Both these actions reduce the pressure within the blood vessels. This means verapamil can be used to lower high blood pressure.

ACE inhibitors such as trandolapril work by blocking the action of a compound in the body called angiotensin converting enzyme (ACE). Normally ACE produces another compound called angiotensin II, as part of the body's natural control of blood pressure.

Angiotensin II causes blood vessels to constrict and narrow, which increases the pressure within the blood vessels. As trandolapril blocks the action of ACE, it reduces the production of angiotensin II. This means that the blood vessels are allowed to relax and widen and the pressure within them therefore falls.

The overall effect of both these medicines is a drop in blood pressure. As they work in different ways they have an additive effect on high blood pressure. The combination is used when high blood pressure has not been lowered sufficiently by taking trandolapril or verapamil alone.

What is it used for?

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

This combination medicine is used for people whose blood pressure is not adequately controlled with either trandolapril or verapamil alone. It will usually only be used once your blood pressure has been stabilised on both trandolapril and verapamil as separate medicines.

Warning!

• Tarka capsules should be swallowed whole and not broken, crushed or chewed.
• You should avoid drinking grapefruit juice while you are taking this medicine, as it may increase the level of verapamil in your blood. This could increase its effect on your blood pressure and make you feel dizzy, and could also increase the risk of experiencing side effects.
• 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.
• If you drink alcohol while taking this medicine you should be aware that verapamil may slow the breakdown of alcohol by the body. This means it could increase the level of alcohol in your blood and its effect. Alcohol may also 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 amount of potassium in your blood should be regularly monitored while you are taking this medicine.

Use with caution in

• Elderly people.
• Decreased kidney function.
• Decreased liver function.
• Slowed conduction of electrical messages between the chambers of the heart (1st degree heart block).
• Slow heart rate (bradycardia).
• People with hardening of the arteries (athersclerosis), eg in the heart (cardiovascular disease), brain (cerebrovascular disease) or legs (peripheral vascular disease).
• Diabetes. (This medicine may enhance the effect of blood sugar lowering medicines - see the end of this factsheet for more information).
• People with low fluid volume or salt levels in the body, eg due to diuretic therapy, low-sodium diet, diarrhoea, vomiting or dehydration.
• Diseases affecting connective tissue, eg scleroderma, systemic lupus erythematosus or rheumatoid arthritis (collagen vascular diseases).
• People receiving therapy to remove certain types of fat from the blood using a machine (LDL apheresis).
• People undergoing therapy to decrease allergy to bee or wasp stings (desensitisation).

Not to be used in

• High blood pressure that is a result of other diseases (secondary hypertension), including high blood pressure caused by compression or blockage of the arteries that carry blood to the kidneys (renovascular hypertension).
• Allergy to other ACE inhibitor medicines, eg captopril.
• 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).
• Failure of the heart to maintain adequate circulation of blood (cardiogenic shock).
• People who have recently had a heart attack (myocardial infarction) that was complicated by a slowed heart rate, heart failure or very low blood pressure.
• Serious defect in the heart's electrical message pathways, resulting in decreased function of the heart (2nd or 3rd degree heart block).
• Failure of the electrical impulse that causes the heart to beat to leave the pacemaker of the heart, resulting in decreased function of the heart (sino-atrial heart block).
• A problem called sick sinus syndrome, which is common in elderly people and is related to poor control of the working of the heart.
• Heart failure.
• People with an abnormal heart rhythm known as atrial flutter or atrial fibrillation, in association with certain other heart rhythm disorders, including Wolff-Parkinson-White syndrome.
• Narrowing of the main artery that leaves the heart to supply blood to the body (aortic stenosis).
• Narrowing of one of the valves in the heart (mitral valve stenosis).
• Heart disease characterised by thickening of the internal heart muscle and a blockage inside the heart (hypertrophic obstructive cardiomyopathy).
• People with severely decreased kidney function, or who are having dialysis for kidney failure.
• People with severely decreased liver function.
• People with fluid in the abdominal cavity (ascites) as a result of liver cirrhosis.
• Overproduction of the steroid hormone aldosterone by the adrenal glands, caused by an abnormality within the glands (primary aldosteronism).
• Hereditary blood disorders called porphyrias.
• Pregnancy.
• Breastfeeding.
• Children and adolescents under 18 years of age.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (Tarka capsules contain lactose).

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.If you feel you have experienced an allergic reaction, stop using 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, you should stop taking it and consult your doctor immediately.
• It is not known if this medicine passes into breast milk. The manufacturer states that it should not be taken by women who are breastfeeding. Women who need treatment with this medicine should not breastfeed. Seek further medical advice from your doctor.

Label warnings

• This medication is to be swallowed whole, not chewed.

Side effects

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

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

• Dizziness or spinning sensation.
• Dry cough.
• Hot flushes.
• Constipation.
• Headache.

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

• Awareness of your heart beat (palpitations).
• Chest pain.
• Slowed conduction of electrical messages between the chambers of the heart (1st degree heart block).
• Skin reaction such as rash, itching, sweating.
• Disturbances of the gut such as diarrhoea, nausea or abdominal pain.
• Tremor.
• Sleepiness.

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

• Loss of appetite.
• Hair loss.

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

• Feeling weak or fatigued.
• Impotence.
• Increased level of potassium in the blood (hyperkalaemia).
• Problems with kidney function.
• Pain in the muscles or joints.
• Shortness of breath.
• Ankle swelling due to fluid retention.
• 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).
• Abnormal heart rate or rhythm (arrhythmias).
• Inability of the heart to pump blood efficiently (heart block or failure).
• Severe drop in blood pressure and fainting.

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult 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 ensure that thecombination is safe.

This medicine will have an additive effect with other medicines thatdecrease blood pressure, particularly other medicines used to treat high bloodpressure (antihypertensives). In people taking antihypertensive medicines itmay cause a large drop in blood pressure with the first dose, particularly inpeople taking diuretic medicines such as furosemide. This may cause dizziness,which can usually be relieved by lying down until the symptoms pass. If you aretaking a diuretic medicine, your doctor may reduce your dose or ask you to stoptaking it for a few days before starting trandolapril. This is to prevent yourblood pressure from dropping too low. If you frequently 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 bloodpressure include the following:

• other ACE inhibitors, eg enalapril
• 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
• other calcium-channel blockers such as 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, diclofenac, ibuprofen) may reduce the blood pressure lowering effect oftrandolapril, and may increase the risk of a decline in kidney function.You should avoid taking this type of painkiller while taking this medicine, unless recommended by your doctor.

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

• angiotensin II receptor antagonists, eg losartan
• ciclosporin
• drospirenone
• epoetin (this may also oppose the blood pressure lowering effect of trandolapril)
• heparin
• potassium-containing salt substitutes (eg Lo-Salt)
• potassium salts, eg potassium citrate for cystitis
• potassium-sparing diuretics (eg spironolactone, triamterene, amiloride)
• potassium supplements.

Trandolapril may increase the blood level of the medicinelithium and for this reason, it is not normally recommended for people takinglithium. If verapamil is taken in combination with lithium the level of lithium in the blood may decrease, which could make it less effective. However, there may also be increased sensitivity to lithium, which could increase the risk of its side effects. People taking this medicine in combination with lithium should havethe level of lithium in their blood closely monitored.

Trandolapril may possibly enhance the blood sugar loweringeffect of insulin and oral antidiabetic medicines, and so could increase therisk of low blood sugar (hypoglycaemia). If you have diabetes your doctor may want you to monitor your blood sugar more frequently when you first start taking this medicine.

There may be an increased risk of a drop in the normal numbersof white blood cells in the blood if trandolapril is taken in combination withany of the 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 an increased risk of a slowed heart rate, low blood pressure and heart failure if beta-blockers (for example atenolol, propranolol, timolol) are used in combination with verapamil. Beta-blocker eye drops (used to treat glaucoma) have also been reported to have this effect. It is recommended that beta-blockers are not given by injection to people taking verapamil.

There may be an increased risk of a slowed heart rate, low blood pressure and heart failure if medicines for irregular heartbeats (antiarrhythmics, for example amiodarone, disopyramide, flecainide) are used in combination with verapamil.

Verapamil may decrease the breakdown of the following medicines by the liver and may therefore increase the amount of these medicines in the blood. As this could increase the risk of their side effects, your doctor may need to reduce your dose of these medicines if you take them in combination with verapamil:

• atorvastatin
• buspirone
• carbamazepine
• ciclosporin
• digoxin
• eplerenone
• imipramine
• ivabradine
• midazolam
• quinidine
• simvastatin
• sirolimus
• tacrolimus
• theophylline.

The following medicines may increase the removal of verapamil from the body and could therefore make it less effective:

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

The following medicines may decrease the removal of verapamil from the body and could therefore increase the chance of its side effects:

• atazanavir
• macrolide antibiotics, eg clarithromycin, erythromycin.

Other medicines containing the same active ingredients

There are currently no other medicines available in the UK that contain both trandolapril and verapamil as the active ingredients.

Goptencontainsjust trandolapril.

Cordilox MR, Securon SR, Univer,Verapress MR,Vertab SR 240 andZolvera all contain just verapamil.

Both trandolapril and verapamil are also available separately as the generic medicines.