Dafiro HCT tablets contain three substances called amlodipine, valsartan and hydrochlorothiazide. All of these substances help to control high blood pressure.
- Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine stops calcium from moving into the blood vessel wall, which stops the blood vessels from tightening.
- Valsartan belongs to a group of substances called “angiotensin-II receptor antagonists”. Angiotensin II is produced by the body and makes the blood vessels tighten, thus increasing the blood pressure. Valsartan works by blocking the effect of angiotensin II.
- Hydrochlorothiazide belongs to a group of substances called “thiazide diuretics”. Hydrochlorothiazide increases urine output, which also lowers blood pressure. As a result of all three mechanisms, the blood vessels relax and blood pressure is lowered.
Dafiro HCT is used to treat high blood pressure in adult patients who are already taking amlodipine, valsartan and hydrochlorothiazide and who may benefit from taking one tablet containing all three substances.
Do not take Dafiro HCT
- if you are more than 3 months pregnant (It is also better to avoid Dafiro HCT in early pregnancy – see Pregnancy section).
- if you are allergic (hypersensitive) to amlodipine, valsartan, hydrochlorothiazide, sulphonamide-derived medicines (medicines used to treat chest or urinary infections), or any of the other ingredients of Dafiro HCT (see section 6, “What Dafiro HCT contains”. If you think you may be allergic, do not take Dafiro HCT and talk to your doctor.
- if you have liver problems, such as liver disorders and jaundice (cholestasis).
- if you have severe kidney problems or if you are having dialysis.
- if you are suffering from an inability to produce urine.
- if the level of potassium or sodium in your blood is too low despite treatment.
- if the level of calcium in your blood is too high despite treatment.
- if you have gout (uric acid crystals in the joints). If any of the above applies to you, do not take Dafiro HCT and talk to your doctor.
Take special care with Dafiro HCT
- if you have a low level of potassium, sodium or magnesium in your blood.
- if you have a high level of calcium in your blood.
- if you are taking medicines or substances that increase the amount of potassium in your blood. These include potassium supplements or salt substitutes containing potassium, potassium-sparing medicines and heparin. It may be necessary to check the amount of potassium in your blood at regular intervals.
- if you have kidney problems, have had a kidney transplant or if you had been told that you have a narrowing of your kidney arteries.
- if you have liver problems.
- if you have or have had heart failure or coronary arterydisease, particularly if you are taking the maximum dose of Dafiro HCT (10 mg/320 mg/25 mg)
- if your doctor has told you that you have a narrowing of the valves in your heart (called “aortic or mitral stenosis”) or that the thickness of your heart muscle is abnormally increased (called “obstructive hypertrophic cardiomyopathy”).
- if you suffer from aldosteronism. This is a disease in which the adrenal glands make too much of the hormone aldosterone If this applies to you, the use of Dafiro HCT is not recommended.
- if you suffer from a disease called systemic lupus erythematosus (also called “lupus” or “SLE”).
- if you have diabetes (high blood sugar).
- if you have high levels of cholesterol or triglycerides in your blood.
- if you experience skin reactions such as rash after sun exposure
- if you had an allergic reaction to other high blood pressure medicines or diuretics (a type of medicine also known as “water tablets”), especially if you suffer from asthma and allergies
- if you have been sick (vomiting or diarrhoea).
- if you experience dizziness and/or fainting during treatment with Dafiro HCT, tell your doctor as soon as possible. If any of these apply to you, talk to your doctor.
You must tell your doctor if you think that you are ( or might become) pregnant. Dafiro HCT is not recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at this stage (see section “Pregnancy and breast-feeding”).
The use of Dafiro HCT in children and adolescents under 18 years of age is not recommended.
Dafiro HCT and older people (age 65 years and older)
Dafiro HCT can be used by people aged 65 years and over at the same dose as for other adults and in the same way as they have already taken the three substances called amlodipine, valsartan and hydrochlorothiazide. Elderly patients, particularly those taking the maximum dose of Dafiro HCT (10 mg/320 mg/25 mg), should have their blood pressure checked regularly.
Using other medicines
Please tell your doctor or pharmacist if you are using or have recently used any other medicine, including medicines obtained without a prescription. Your doctor may need to change the dose or take other precautions. In some cases you may have to stop using one of the medicines. This is especially important if you are using any of the medicines listed below:
Do not take together with:
- lithium (a medicine used to treat some types of depression);
- medicines or substances that increase the amount of potassium in your blood. These include potassium supplements or salt substitutes containing potassium, potassium-sparing medicines and heparin.
Caution should be used with:
- alcohol, sleeping pills and anaesthetics (medicines allowing patients to undergo surgery and other procedures);
- allopurinol (anti-gout treatment);
- amantadine (anti-Parkinson therapy, also used for influenza treatment);
- anticholinergic agents (medicines used to treat a variety of disorders such as gastrointestinal cramps, urinary bladder spasm, asthma, motion sickness, muscular spasms, Parkinson's disease and as an aid to anaesthesia);
- anticonvulsant medicines and mood-stabilising medicines used to treat epilepsy and bipolar disorder (e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone);
- cholestyramine and colestipol (substances used mainly to treat high levels of lipids in the blood);
- ciclosporin (a medicine used in transplantation to prevent organ rejection or for other conditions, e.g: rheumatoid arthritis or atopic dermatitis);
- cortisone-like medicines, steroids;
- curare derivatives (a medicine to relax the muscles which is used during operations);
- cytotoxic medicines (used to treat cancer);
- digoxin (a heart medicine);
- medicines for the treatment of diabetes (oral agents such as metformin or insulins);
- medicines to increase blood pressure (adrenaline, noradrenaline);
- medicines used for HIV/AIDS (e.g. ritonavir) or for treatment of fungal infections (e.g. ketoconazole);
- medicines used for oesophageal ulceration and inflammation (carbenoxolone);
- medicines used to relieve pain or inflammation, especially non-steroidal anti-inflammatory agents;
- nitroglycerin and other nitrates, or other substances called “vasodilators”;
- other medicines to treat high blood pressure (beta blockers, diazoxides, methyldopa);
- rifampicin (used, for example, to treat tuberculosis);
- some medicines used to treat infections such as amphotericin, penicillin G, tetracycline;
- St. John’s wort;
- vitamin D and calcium salts. Talk to your doctor before drinking alcohol. Alcohol may make your blood pressure fall too much and/or increase the possibility of dizziness or fainting.
Taking Dafiro HCT with food and drink
You can take Dafiro HCT with or without food.
Pregnancy and breast-feeding
You must tell your doctor if you think you are ( or might become) pregnant. Your doctor will normally advise you to stop taking Dafiro HCT before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Dafiro HCT. Dafiro HCT is not recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if it is used after the third month of pregnancy.
Breast-feeding Tell your doctor if you are breast-feeding or about to start breast-feeding. Dafiro HCT is not recommended for mothers who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if your baby is a newborn, or was born prematurely.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
As with many other medicines used to treat high blood pressure, this medicine may make you feel dizzy. If you experience this symptom, do not drive or use tools or machines.
Always take this medicine exactly as your doctor has told you. You should check with your doctor if you are not sure. This will help you get the best results and lower the risk of side effects.
The usual dose of Dafiro HCT is one tablet per day.
- It is best to take the tablet at the same time each day. Morning is the best time.
- Swallow the tablet whole with a glass of water.
- You can take Dafiro HCT with or without food.
Depending on how you respond to the treatment, your doctor may suggest a higher or lower dose.
If you take more Dafiro HCT than you should
If you have accidentally taken too many Dafiro HCT tablets, talk to a doctor immediately.You may require medical attention.
If you forget to take Dafiro HCT
If you forget to take a dose of this medicine, take it as soon as you remember and then take the next dose at its usual time. If it is almost time for your next dose you should simply take the next tablet at the usual time. Do not take a double dose (two tablets at once) to make up for a forgotten tablet.
If you stop taking Dafiro HCT
Stopping your treatment with Dafiro HCT may cause your disease to get worse. Do not stop taking your medecine unless your doctor tells you to.
Always take this medicine, even if you are feeling well
People who have high blood pressure often do not notice any signs of the problem. Many feel normal. It is very important that you take this medicine exactly as your doctor tells you to get the best results and reduce the risk of side effects. Keep your appointments with the doctor even if you are feeling well.
If you have any further questions on the use of this product ask your doctor or pharmacist.
Like all medicines, Dafiro HCT can cause side effects, although not everybody gets them. These side effects may occur with certain frequencies, which are defined as follows: very common: affects more than 1 user in 10
common: affects 1 to 10 users in 100
uncommon: affects 1 to 10 users in 1,000
rare: affects 1 to 10 users in 10,000
very rare: affects less than 1 user in 10,000
not known: frequency cannot be estimated from the available data
Some side effects can be serious and need immediate medical attention:
You should see your doctor immediately if you experience any of the following symptoms: Common
- low blood pressure (feeling of faintness, light-headedness, sudden loss of consciousness) Uncommon
- severely decreased urine output (decreased kidney function)
- spontaneous bleeding
- irregular heart beat
- liver disorder Very rare
- allergic reaction with symptoms such as rash, itching
- angioedema: swelling of face or lips or tongue, difficulty of breathing
- crushing/tight chest pain that gets worse or that does not go away
- weakness, bruising, fever and frequent infections
Other possible side effects of Dafiro HCT:
Common: Stomach discomfort after meal; tiredness; swelling; low level of potassium in the blood; headache; frequent urination.
Uncommon: Fast heart beat; spinning sensation; vision disorder; stomach discomfort; chest pain; increase of urea nitrogen, creatinine and uric acid in the blood; high level of calcium fat or sodium in the blood; decrease of potassium in the blood; breath odour; diarrhoea; dry mouth; nausea; vomiting; abdominal pain; weight increase; loss of appetite; disturbed sense of taste; back pain; joint swelling; muscle cramps/weakness/pain; pain in extremity; inability to either stand or walk in a normal manner; weakness; abnormal coordination; dizziness on standing up or after exercising; lack of energy; sleep disturbances; tingling or numbness; neuropathy; sleepiness; sudden, temporary loss of consciousness; low blood pressure on standing up; impotence; cough; breathlessness; throat irritation; excessive sweating; itching; swelling, reddening and pain along a vein; skin reddening; trembling. Not known: Changes in blood tests for kidney function, increase of potassium in your blood, low level of red blood cells.
Side effects reported with amlodipine or valsartan or hydrochlorothiazide alone, but not observed with Dafiro HCT or observed in a higher frequency:
Amlodipine Common: Palpitations; abdominal pain; nausea; sleepiness; hot flushes.
Uncommon: Ringing noise in ears; change of bowel habit; pain; weight decrease; joint pain; trembling; mood swings; urination disorders; urination at night; breast enlargement in men; runny nose; hair loss; skin eruption; purple skin patches; rash; skin discoloration.
Very rare: Low level of white blood cells and blood platelets; irregular heart beat; heart attack; inflammation of the stomach lining or of the pancreas, gingival overgrowth, abnormal liver function test; liver disorder which can occur together with yellow skin and eyes, or dark-coloured urine; allergic reaction including swelling deeper in the skin and difficulty breathing; high level of sugar in the blood; increased muscle stiffness; skin reaction with skin reddening and peeling, blistering of lips, eyes or mouth; itchy rash; inflammation of blood vessels.
Not known: Stiff limbs and trembling hands.
Valsartan Not known: Abnormal red blood cell test; low level of a certain type of white blood cell and blood platelet; increase of potassium in the blood; increase of creatinine in the blood; abnormal liver function test; allergic reaction including swelling deeper in the skin and difficulty breathing; muscle pain; severely decreased urine output; itching; rash; inflammation of blood vessels.
Hydrochlorothiazide Common: Increase of lipids in the blood.
Uncommon: Low level of magnesium in the blood; rash; itchy rash.
Rare: Low level of blood platelets, sugar in the urine; high level of sugar in the blood; depression; irregular heart beat; abdominal discomfort; constipation; liver disorder which can occur together with yellow skin and eyes, or dark-coloured urine; increased sensitivity of skin to sun; purple skin patches.
Very rare: Lack or low level of white blood cells; haemolytic anaemia (abnormal breakdown of red blood cells either in the blood vessels or elsewhere in the body); inflammation of the pancreas; allergic reaction; difficulty breathing, breathlessness; inflammation of the lungs, lupus erythematosus; inflammation of blood vessels; severe skin disease that causes rash, red skin, blistering of the lips, eyes or mouth, skin peeling, fever.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Keep out of the reach and sight of children.
Do not use Dafiro HCT after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.
Do not store above 30°C.
Store in the original package in order to protect from moisture.
Do not use any Dafiro HCT pack that is damaged or shows signs of tampering.
Dafiro HCT is a medicine that contains three active substances, amlodipine, valsartan and hydrochlorothiazide. It is available as tablets containing amlodipine, valsartan and hydrochlorothiazide in the following amounts: 5/160/12.5 mg, 10/160/12.5 mg, 5/160/25 mg; 10/160/25 mg and 10/320/25 mg.
Dafiro HCT is used to treat essential hypertension (high blood pressure) in adults whose blood pressure is already adequately controlled with a combination of amlodipine, valsartan and hydrochlorothiazide. ‘Essential’ means that the hypertension has no obvious cause. The medicine can only be obtained with a prescription.
Dafiro HCT is taken by mouth as one tablet once a day, at the same time of the day and preferably in the morning. The dose of Dafiro HCT to be used is the same as the doses of three individual active substances that the patient was taking before. The daily dose of Dafiro HCT should not exceed 10 mg of amlodipine, 320 mg of valsartan and 25 mg of hydrochlorothiazide.
The three active substances in Dafiro HCT are anti-hypertensive medicines that are already in use in the European Union (EU).
Amlodipine is a ‘calcium channel blocker’. It blocks special channels on the surface of cells called calcium channels, through which calcium ions normally enter the cells. When calcium ions enter the cells in the muscles of blood vessel walls, this causes contraction. By reducing the flow of calcium into the cells, amlodipine prevents the cells from contracting and helps the blood vessel walls to relax and widen, thereby reducing blood pressure.
Valsartan is an ‘angiotensin II receptor antagonist’, which means that it blocks the action of a body hormone called angiotensin II. Angiotensin II is a powerful vasoconstrictor (a substance that narrows blood vessels). By blocking the receptors to which angiotensin II normally attaches, valsartan stops the hormone having an effect, allowing the blood vessels to widen and blood pressure to reduce. Hydrochlorothiazide is a diuretic. It works by increasing urine output, reducing the volume of fluid in the blood and lowering the blood pressure.
The combination of the three active substances has an additive effect, reducing the blood pressure more than the individual medicines alone. By lowering the blood pressure, the risks associated with high blood pressure, such as having a stroke, are reduced.
Because the combination of the three active substances has been in use for a number of years, the company presented studies showing that the tablet containing all three substances is absorbed in the body in the same way as the separate tablets.
In addition, one main study was carried out in 2,271 patients with moderate to severe hypertension with the highest strength of Dafiro HCT (320 mg valsartan, 10 mg amlodipine and 25 mg hydrochlorothiazide). Patients received either Dafiro HCT or one of the three combinations containing only two of the active substances for eight weeks. The main measure of effectiveness was the average change in the blood pressure.
Treatment with the highest strength of Dafiro HCT was more effective at treating hypertension than dual combinations containing any of the two active substances. The average reduction in blood pressure was around 39.7/24.7 mmHg in patients taking Dafiro HCT compared with 32/19.7 mmHg, 33.5/21.5 mmHg and 31.5/19.5 mmHg in patients taking valsartan/hydrochlorothiazide, valsartan/amlodipine and hydrochlorothiazide/amlodipine combinations, respectively.
The most common side effects with Dafiro HCT (seen in between 1 and 10 patients in 100) are hypokalaemia (low blood potassium levels), dizziness, headache, hypotension (low blood pressure), dyspepsia (heartburn), pollakiuria (abnormally frequent urination), fatigue (tiredness) and oedema (fluid retention). For the full list of all side effects reported with Dafiro HCT, see the Package Leaflet. Dafiro HCT should not be used in people who may be hypersensitive (allergic) to the active substances, to other sulfonamides, to dihydropyridine derivatives or to any of the other ingredients in Dafiro HCT. It must not be used in women who are more than three months pregnant. It must also not be used in patients who have liver or bile problems (such as jaundice), severe kidney problems, anuria (a condition in which a patient cannot make or pass urine) or in patients undergoing dialysis (a blood clearance technique). Finally, Dafiro HCT must not be used in patients with hypokalaemia (low blood potassium levels), hyponatraemia (low blood sodium levels) and hypercalcaemia (high blood calcium levels) that do not respond to treatment and in patients with hyperuricaemia (high blood levels of uric acid) that causes symptoms.
The Committee for Medicinal Products for Human Use (CHMP) noted that patients already taking the three active substances would be more likely to comply with their treatment if prescribed Dafiro HCT which combines the three substances in a single tablet. The main study showed the benefit of the highest strength of Dafiro HCT in lowering the blood pressure. For all doses, Dafiro HCT also met requirements to prove that it was comparable to the combinations of the individual active substances taken seperately. The CHMP therefore decided that Dafiro HCT’s benefits are greater than its risks for the treatment of essential hypertension in adults whose blood pressure is already adequately controlled with a combination of amlodipine, valsartan and hydrochlorothiazide. The Committee recommended that Dafiro HCT be given marketing authorisation.
The European Commission granted a marketing authorisation valid throughout the European Union for Dafiro HCT to Novartis Europharm Limited on 4 November 2009.