Ifirmacombi 300 mg/12.5 mg film-coated tablets

Ifirmacombi 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 Ifirmacombi work together to lower blood pressure further than if either was given alone.

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

Do not take Ifirmacombi

• if you are allergic (hypersensitive) to irbesartan or any of the other ingredients of Ifirmacombi
• if you are allergic (hypersensitive) to hydrochlorothiazide or any other sulphonamide-derived medicines
• if you are more than 3 months pregnant. (It is also better to avoid Ifirmacombi 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

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

Take special care with Ifirmacombi

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. Ifirmacombi 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 Ifirmacombi)
• 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 Ifirmacombi may have an effect on other medicines. Preparations containing lithium should not be taken with Ifirmacombi 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, and medicines to treat cancer, pain killers, arthritis medicines or colestyramine and colestipol resins for lowering blood cholesterol.

Taking Ifirmacombi with food and drink

Ifirmacombi can be taken with or without food.

Due to the hydrochlorothiazide contained in Ifirmacombi, 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 Ifirmacombi before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Ifirmacombi. Ifirmacombi 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. Ifirmacombi 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. Ifirmacombi 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.

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

Dosage of Ifirmacombi 150 mg/12.5 mg

The usual dose of Ifirmacombi 150 mg/12.5 mg is one tablet a day. Ifirmacombi 150 mg/12.5 mg 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 Ifirmacombi. If this dose does not help to reduce your blood pressure as required, the doctor may prescribe Ifirmacombi 300 mg/12.5 mg to you.

Dosage of Ifirmacombi 300 mg/12.5 mg

The usual dose of Ifirmacombi 300 mg /12.5 mg is one tablet a day.
Ifirmacombi 300 mg/12.5 mg 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 Ifirmacombi.
If this dose does not help to reduce your blood pressure as required, the doctor may prescribe Ifirmacombi 300 mg/25 mg to you.

Dosage of Ifirmacombi 300 mg/25 mg

The usual dose of Ifirmacombi 300 mg/25 mg is one tablet a day. This dose should not be increased. Ifirmacombi 300 mg/25 mg 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 Ifirmacombi.
If this medicine does not help to reduce your blood pressure as required, the doctor will prescribe additional treatment to you.

Method of administration

Ifirmacombi is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of water). You can take Ifirmacombi 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 Ifirmacombi 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 Ifirmacombi than you should

If you accidentally take too many tablets, contact your doctor immediately.

Children should not take Ifirmacombi

Ifirmacombi 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 Ifirmacombi

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.

Like all medicines, Ifirmacombi 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 Ifirmacombi and contact your doctor immediately.

Side effects are classified into the following groups in order of frequency 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 available data

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

Common side effects

• 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

• 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 the combination of Irbesartan and Hydrochlorothiazide The frequency of these effects is not known. These side 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.

Keep out of the reach and sight of children.

Do not use Ifirmacombi after the expiry date which is stated on the packaging after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

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 Ifirmacombi contains

• The active substances are irbesartan and hydrochlorothiazide. Each Ifirmacombi 150 mg/12.5 mg film-coated tablet contains 150 mg irbesartan (as irbesartan hydrochloride) and 12.5 mg hydrochlorothiazide.

Each Ifirmacombi 300 mg/12.5 mg film-coated tablet contains 300 mg irbesartan (as irbesartan hydrochloride) and 12.5 mg hydrochlorothiazide.
Each Ifirmacombi 300 mg/25 mg film-coated tablet contains 300 mg irbesartan (as irbesartan hydrochloride) and 25 mg hydrochlorothiazide.

• The other ingredients are: Ifirmacombi 150 mg/12.5 mg: mannitol, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, sodium starch glycolate, talc, macrogol 6000, hydrogenated castor oil in the tablet core and polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, yellow iron oxide (E172) and red iron oxide (E172) in the film-coating.

Ifirmacombi 300 mg/12.5 mg:
mannitol, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, sodium starch glycolate, talc, macrogol 6000, hydrogenated castor oil in the tablet core and polyvinyl alcohol, titanium dioxide (E171), macrogol, talc in the film-coating.

Ifirmacombi 300 mg/25 mg:
mannitol, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, sodium starch glycolate, talc, macrogol 6000, hydrogenated castor oil in the tablet core and polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, yellow iron oxide (E172) and red iron oxide (E172) in the film-coating.

What Ifirmacombi looks like and contents of the pack

Ifirmacombi 150 mg/12.5 mg
Pale pink, biconvex, oval, film-coated tablets (tablets).

Ifirmacombi 300 mg/12.5 mg
White, biconvex, capsule shaped, film-coated tablets (tablets).

Ifirmacombi 300 mg/25 mg
Pale pink, biconvex, capsule shaped, film-coated tablets (tablets).

Boxes of 14, 28, 30, 56, 56 x 1, 84, 90 and 98 film-coated tablets in blisters are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder

KRKA, d.d., Novo mesto, ?marje?ka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer

KRKA, d.d., Novo mesto, ?marje?ka cesta 6, 8501 Novo mesto, Slovenia

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien KRKA, d.d., Novo mesto TélTel 32 03 321 63 52 LuxembourgLuxemburg KRKA, d.d., Novo mesto TélTel 32 03 321 63 52

KRKA Te. 359 02 962 34 50 Magyarország KRKA Magyarország Kereskedelmi Kft. Tel. 361 0 355 8490

eská republika KRKA R, s.r.o. Tel 420 0 221 115 150 Malta KRKA Pharma Dublin, Ltd. Tel 46 8 643 67 66

Danmark KRKA Sverige AB Tlf 46 08 643 67 66 SE Nederland KRKA, d.d., Novo mesto Tel 32 3 321 63 52 BE

Deutschland TAD Pharma GmbH Tel 49 0 4721 6060 Norge KRKA Sverige AB Tlf 46 08 643 67 66 SE

Eesti KRKA, d.d., Novo mesto Eesti filiaal Tel 372 0 6 671 658 Österreich KRKA Pharma GmbH, Wien Tel 43 01 66 24 300

QUALIA PHARMA S.A. 30 0210 2832941 Polska KRKA-POLSKA Sp. z o.o. Tel. 48 022 573 7500

España KRKA, d.d., Novo mesto Tel 34 061 5089 809 Portugal KRKA Farmacêutica, Unipessoal Lda. Tel 351 021 46 43 650

France KRKA, d.d., Novo mesto Tél 32 3 321 63 52 BE România KRKA Romania S.R.L., Bucharest Tel 402 01 310 66 05

Ireland KRKA Pharma Dublin, Ltd. Tel 46 8 643 67 66 Slovenija KRKA, d.d., Novo mesto Tel 386 0 1 47 51 100

Ísland KRKA Sverige AB Sími 46 08 643 67 66 SE Slovenská republika KRKA Slovensko, s.r.o., Tel 421 0 2 571 04 501

Italia KRKA, d.d., Novo mesto Tel 39 069448827 SuomiFinland KRKA Sverige AB PuhTel 46 08 643 67 66 SE

Kipa Pharmacal Ltd. 357 24 651 882 Sverige KRKA Sverige AB Tel 46 08 643 67 66 SE

Latvija KRKA, d.d., Novo mesto Tel 371 6 733 86 10 United Kingdom Consilient Health UK Ltd. Tel 44 02089562310

Lietuva

UAB KRKA LietuvaTel: + 370 5 236 27 40

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