Karvezide 300 mg/25 mg film-coated tablets

 

What is it and how is it used?

Karvezide is a combination of two active substances, irbesartan and hydrochlorothiazide. Irbesartan belongs to a group of medicines known as angiotensin-II receptor antagonists. Angiotensin-II is a substance produced in the body that binds to receptors in blood vessels causing them to tighten. This results in an increase in blood pressure. Irbesartan prevents the binding of angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. Hydrochlorothiazide is one of a group of medicines (called thiazide diuretics) that causes increased urine output and so causes a lowering of blood pressure.
The two active ingredients in Karvezide work together to lower blood pressure further than if either was given alone.

Karvezide is used to treat high blood pressure, when treatment with irbesartan or hydrochlorothiazide alone did not provide adequate control of your blood pressure.

What do you have to consider before using it?

Do not take Karvezide
if you are allergic (hypersensitive) to irbesartan or any of the other ingredients of Karvezide if you are allergic (hypersensitive) to hydrochlorothiazide or any other sulfonamide-derived medicines
if you are more than 3 months pregnant. (It is also better to avoid Karvezide in early pregnancy – see pregnancy section)
if you have severe liver or kidney problems
if you have difficulty in producing urine
if your doctor determines that you have persistently high calcium or low potassium levels in your blood

Karvezide should not be given to children and adolescents (under 18 years).

Take special care with Karvezide
Tell your doctor
if any of the following apply to you:
if you get excessive vomiting or diarrhoea
if you suffer from kidney problems or have a kidney transplant
if you suffer from heart problems
if you suffer from liver problems
if you suffer from diabetes
if you suffer from lupus erythematosus (also known as lupus or SLE)
if you suffer from primary aldosteronism (a condition related to high production of the hormone aldosterone, which causes sodium retention and, in turn, an increase in blood pressure).

You must tell your doctor if you think you are ( or might become) pregnant. Karvezide 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 that stage (see pregnancy section).

You should also tell your doctor:
if you are on a low-salt diet
if you have signs such as abnormal thirst, dry mouth, general weakness, drowsiness, muscle pain or cramps, nausea, vomiting, or an abnormally fast heart beat which may indicate an excessive effect of hydrochlorothiazide (contained in Karvezide)
if you experience an increased sensitivity of the skin to the sun with symptoms of sunburn (such as redness, itching, swelling, blistering) occurring more quickly than normal if you are going to have an operation (surgery) or be given anaesthetics

The hydrochlorothiazide contained in this medicine could produce a positive result in an anti-doping test.

Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Diuretic agents such as the hydrochlorothiazide contained in Karvezide may have an effect on other medicines. Preparations containing lithium should not be taken with Karvezide without close supervision by your doctor.

You may need to have blood checks if you take:
potassium supplements
salt substitutes containing potassium
potassium sparing medicines or other diuretics (water tablets)
some laxatives
medicines for the treatment of gout
therapeutic vitamin D supplements
medicines to control heart rhythm
medicines for diabetes (oral agents or insulins)

It is also important to tell your doctor if you are taking other medicines to reduce your blood pressure, steroids, medicines to treat cancer, pain killers, arthritis medicines, or colestyramine and colestipol resins for lowering blood cholesterol.

Taking Karvezide with food and drink
Karvezide can be taken with or without food.

Due to the hydrochlorothiazide contained in Karvezide, if you drink alcohol while on treatment with this medicine, you may have an increased feeling of dizziness on standing up, specially when getting up from a sitting position.

Pregnancy and breast-feeding
Pregnancy
You must tell your doctor if you think you are ( or might become) pregnant. Your doctor will normally advise you to stop taking Karvezide before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Karvezide. Karvezide is not recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy.

Breast-feeding
Tell your doctor if you are breast-feeding or about to start breast-feeding. Karvezide 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 newborn, or was born prematurely.

Driving and using machines
No studies on the effects on the ability to drive and use machines have been performed. Karvezide is unlikely to affect your ability to drive or use machines. However, occasionally dizziness or weariness may occur during treatment of high blood pressure. If you experience these, talk to your doctor before attempting to drive or use machines.

Important information about some of the ingredients of Karvezide
Karvezide contains lactose
. If you have been told by your doctor that you have an intolerance to some sugars (e.g. lactose), contact your doctor before taking this medicine.

How is it used?

Always take Karvezide exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Dosage
The usual dose of Karvezide is one tablet a day. Karvezide will usually be prescribed by your doctor when your previous treatment did not reduce your blood pressure enough. Your doctor will instruct you how to switch from the previous treatment to Karvezide.

Method of administration
Karvezide is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of water). You can take Karvezide with or without food. Try to take your daily dose at about the same time each day. It is important that you continue to take Karvezide until your doctor tells you otherwise.

The maximal blood pressure lowering effect should be reached 6-8 weeks after beginning treatment.

If you take more Karvezide than you should
If you accidentally take too many tablets, contact your doctor immediately.

Children should not take Karvezide
Karvezide should not be given to children under 18 years of age. If a child swallows some tablets, contact your doctor immediately.

If you forget to take Karvezide
If you accidentally miss a daily dose, just take the next dose as normal. Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

What are possible side effects?

Like all medicines, Karvezide can cause side effects, although not everybody gets them. Some of these effects may be serious and may require medical attention.

Rare cases of allergic skin reactions (rash, urticaria), as well as localised swelling of the face, lips and/or tongue have been reported in patients taking irbesartan.

If you get any of the above symptoms or get short of breath, stop taking Karvezide and contact your doctor immediately.

Side effects reported in clinical studies for patients treated with Karvezide were:

Common side effects (affect 1 to 10 users in 100)nausea/vomiting
abnormal urination
fatigue
dizziness (including when getting up from a lying or sitting position)
blood tests may show raised levels of an enzyme that measures the muscle and heart function (creatine kinase) or raised levels of substances that measure kidney function (blood urea nitrogen, creatinine).
If any of these side effects causes you problems, talk to your doctor.

Uncommon side effects (affect 1 to 10 users in 1,000)
diarrhoea
low blood pressure
fainting
heart rate increased
flushing
swelling
sexual dysfunction (problems with sexual performance)
blood tests may show lowered levels of potassium and sodium in your blood. If any of these side effects causes you problems, talk to your doctor.

Side effects reported since the launch of Karvezide
The frequency of these effects is not known. These undesirable effects are: headache, ringing in the ears, cough, taste disturbance, indigestion, pain in joints and muscles, liver function abnormal and impaired kidney function, increased level of potassium in your blood and allergic reactions such as rash, hives, swelling of the face, lips, mouth, tongue or throat.

As for any combination of two active substances, side effects associated with each individual component cannot be excluded.
Side effects associated with irbesartan alone
In addition to the side effects listed above, chest pain has also been reported.
Side effects associated with hydrochlorothiazide alone
Loss of appetite; stomach irritation; stomach cramps; constipation; jaundice (yellowing of the skin and/or whites of the eyes); inflammation of the pancreas characterised by severe upper stomach pain, often with nausea and vomiting; sleep disorders; depression; blurred vision; lack of white blood cells, which can result in frequent infections, fever; decrease in the number of platelets (a blood cell essential for the clotting of the blood), decreased number of red blood cells (anaemia) characterised by tiredness, headaches, being short of breath when exercising, dizziness and looking pale; kidney disease; lung problems including pneumonia or build-up of fluid in the lungs; increased sensitivity of the skin to the sun; inflammation of blood vessels; a skin disease characterized by the peeling of the skin all over the body; cutaneous lupus erythematosus, which is identified by a rash that may appear on the face, neck, and scalp; allergic reactions; weakness and muscle spasm; altered heart rate; reduced blood pressure after a change in body position; swelling of the salivary glands; high sugar levels in the blood; sugar in the urine; increases in some kinds of blood fat; high uric acid levels in the blood, which may cause gout.

It is known that side effects associated with hydrochlorothiazide may increase with higher doses of hydrochlorothiazide.

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.

How should it be stored?

Keep out of the reach and sight of children.

Do not use Karvezide after the expiry date which is stated on the carton and on the 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.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What is it?

Karvezide is a medicine that contains two active substances, irbesartan and hydrochlorothiazide. It is available as oval tablets (peach: 150 mg or 300 mg irbesartan and 12.5 mg hydrochlorothiazide; pink: 300 mg irbesartan and 25 mg hydrochlorothiazide).

What is it used for?

Karvezide is used in adults who have essential hypertension (high blood pressure) that is not adequately controlled by irbesartan or hydrochlorothiazide alone. ‘Essential’ means that the hypertension has no obvious cause.
The medicine can only be obtained with a prescription.

How is it used?

Karvezide is taken by mouth, with or without food. The dose of Karvezide to be used depends on the dose of irbesartan or hydrochlorothiazide that the patient was taking before. Doses higher than 300 mg irbesartan and 25 mg hydrochlorothiazide once a day are not recommended. Karvezide may be added to other treatments for hypertension.

How does it work?

Karvezide contains two active substances, irbesartan and hydrochlorothiazide.
Irbesartan is an ‘angiotensin II receptor antagonist’, which means that it blocks the action of a hormone in the body 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, irbesartan stops the hormone having an effect, allowing the blood vessels to widen. Hydrochlorothiazide is a diuretic, which is another type of treatment for hypertension. It works by increasing urine output, reducing the amount of fluid in the blood and lowering the blood pressure. The combination of the two active substances has an additive effect, reducing the blood pressure more than either medicine alone. By lowering the blood pressure, the risks associated with high blood pressure, such as having a stroke, are reduced.

How has it been studied?

Irbesartan on its own has been approved in the European Union (EU) since 1997 under the names Karvea and Aprovel. It can be used with hydrochlorothiazide to treat hypertension. The studies of

Karvea/Aprovel used with hydrochlorothiazide as separate tablets were used to support the use of Karvezide. Further studies were also carried out with doses of 300 mg irbesartan in combination with 25 mg hydrochlorothiazide. The main measure of effectiveness was the reduction in diastolic blood pressure (the blood pressure measured between two heartbeats).

What benefits has it shown during the studies?

Karvezide was more effective than placebo (a dummy treatment) and than hydrochlorothiazide alone in reducing diastolic blood pressure. Increasing the dose to 300 mg irbesartan and 25 mg hydrochlorothiazide may give a further decrease in blood pressure.

What is the risk associated?

The most common side effects with Karvezide (seen in between 1 and 10 patients in 100) are dizziness, nausea (feeling sick) or vomiting, abnormal urination, fatigue (tiredness), and increases in blood urea nitrogen (BUN, a breakdown product of protein), creatinine (a breakdown product of muscle) and creatine kinase (an enzyme found in muscles). For the full list of all side effects reported with Karvezide, see the Package Leaflet.
Karvezide should not be used in people who may be hypersensitive (allergic) to irbesartan, hydrochlorothiazide, sulfonamides, or any of the other ingredients. It must not be used in women who are more than three months pregnant. Its use during the first three months of pregnancy is not recommended. Karvezide must also not be used in patients who have severe liver, kidney or bile problems, blood potassium levels that are too low or blood calcium levels that are too high. Care must be taken when using Karvezide with other medicines that have an effect on blood potassium levels. The full list of these medicines is given in the Package Leaflet.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Karvezide’s benefits are greater than its risks for the treatment of essential hypertension in adult patients whose blood pressure is not adequately controlled on irbesartan or hydrochlorothiazide alone. The Committee recommended that Karvezide be given marketing authorisation.

Further information

The European Commission granted a marketing authorisation valid throughout the EU for Karvezide to Bristol-Myers Squibb Pharma EEIG on 16 October 1998. The marketing authorisation was renewed on 16 October 2003 and on 16 October 2008.