IfirmacomBi

Package leaflet: Information for the patient

Ifirmacombi 150 mg/12.5 mg film-coated tablets, 300 mg/12.5 mg film-coated tablets, 300 mg/25 mg film-coated tablets

irbesartan/hydrochlorothiazide
Read this leaflet carefully before taking this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If any of the side effects worsens, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist. See section 4. Contents of this leaflet:
  1. What Ifirmacombi is and what it is used for
  2. What you need to know before taking Ifirmacombi
  3. How to take Ifirmacombi
  4. Possible side effects
  5. How to store Ifirmacombi
  6. Further information

1. What Ifirmacombi is and what it is used for

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 its receptors located in the blood vessels, causing them to narrow. This leads to an increase in blood pressure. Irbesartan prevents angiotensin-II from binding to its receptors, resulting in relaxation of the blood vessels and a reduction in blood pressure.
Hydrochlorothiazide belongs to a group of medicines (so-called thiazide diuretics) that increase urine production, thereby lowering blood pressure.
The two active substances in Ifirmacombi work together to lower blood pressure to a greater extent than either medicine alone.
Ifirmacombi is used to treat high blood pressure when irbesartan or hydrochlorothiazide alone have not adequately controlled blood pressure.

2. What you need to know before taking Ifirmacombi

Do not take Ifirmacombi

• If you are allergic to irbesartan or to any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to hydrochlorothiazide or to any sulfonamide-derived medicines
• If you are more than 3 months pregnant (it is better to avoid taking Ifirmacombi even in early pregnancy – see section “Pregnancy”)
• If you have severe liver or kidney problems
• If you have difficulty urinating
• If your doctor has diagnosed you with persistently high calcium levels or low potassium levels in your blood
• If you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren

Warnings and precautions

Talk to your doctor before taking Ifirmacombi if you are in any of the following situations:

• If you have excessive vomiting or diarrhea
• If you have kidney disorders or have had a kidney transplant
• If you have heart problems
• If you have liver problems
• If you have diabetes
• If you develop low blood sugar levels (symptoms may include sweating, weakness, hunger, dizziness, trembling, headache, flushing or paleness, numbness, rapid and pounding heartbeat), especially if you are being treated for diabetes
• If you have systemic lupus erythematosus (also known as lupus or SLE)
• If you have primary hyperaldosteronism (a condition involving excessive production of the hormone aldosterone, leading to sodium retention and subsequent increase in blood pressure)
• If you have previously had skin cancer or develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from exposure to sunlight and UV radiation while taking Ifirmacombi.
• If you have previously experienced respiratory or lung problems (including inflammation or fluid accumulation in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulties after taking Ifirmacombi, consult a doctor immediately.
• If you are taking any of the following medicines for high blood pressure:
  • an "ACE inhibitor" (e.g., enalapril, lisinopril, ramipril), especially if you have kidney problems related to diabetes,
  • aliskiren. Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g., potassium) at regular intervals. See also the section "Do not take Ifirmacombi". You must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Ifirmacombi is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn child if taken during this period (see section “Pregnancy”).

Also, inform your doctor:

• If you are on a low-salt diet
• If you experience symptoms such as excessive thirst, dry mouth, general weakness, drowsiness, muscle pain or cramps, nausea, vomiting, or an abnormally fast heartbeat, which may indicate an excessive effect of hydrochlorothiazide (contained in Ifirmacombi)
• If you notice increased skin sensitivity to sunlight, with symptoms of sunburn (such as redness, itching, swelling, rash) occurring more quickly than usual
• If you are scheduled for surgery or need to take anesthetics
• If you experience changes in vision or pain in one or both eyes while taking Ifirmacombi. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure (glaucoma), which may occur from a few hours to several weeks after taking Ifirmacombi. If left untreated, these symptoms may lead to permanent vision loss. If you have previously had an allergy to penicillin or sulfonamides, you may be at higher risk of developing these symptoms. You should stop treatment with Ifirmacombi and consult your doctor immediately.

Hydrochlorothiazide, contained in this medicine, may lead to positive results in anti-doping tests.

Children and adolescents

Ifirmacombi must not be given to children and adolescents (under 18 years of age).

Other medicines and Ifirmacombi

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Diuretics such as hydrochlorothiazide contained in Ifirmacombi may interact with other medicines. Preparations containing lithium should not be taken together with Ifirmacombi unless under strict medical supervision.

Your doctor may need to adjust your dose and/or take additional precautions:

• If you are taking an ACE inhibitor or aliskiren (see also sections: "Do not take Ifirmacombi" and "Warnings and precautions").

You may need blood tests if you are using:

• potassium supplements
• salt substitutes containing potassium
• potassium-sparing diuretics or other diuretics
• certain laxatives
• medicines for the treatment of gout
• vitamin D supplements
• medicines to control heart rhythm
• medicines for diabetes (oral medications such as repaglinide or insulin)
• carbamazepine (a medicine used to treat epilepsy)

It is also important to inform your doctor if you are taking other medicines to lower blood pressure, steroids, cancer treatment medicines, painkillers, medicines for arthritis, or colestyramine and colestipol to lower cholesterol levels in the blood.

Ifirmacombi with food, drinks and alcohol

Ifirmacombi can be taken with or without food. Due to the hydrochlorothiazide contained in Ifirmacombi, drinking alcohol during treatment with this medicine may make you feel more dizzy, especially when standing up from a sitting position.

Pregnancy and breastfeeding

Pregnancy

Inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Ifirmacombi before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine. Ifirmacombi is not recommended during pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn child if taken after the third month of pregnancy.

Breast-feeding

Inform your doctor if you are breast-feeding or planning to breast-feed. Ifirmacombi is not recommended for women who are breast-feeding, and your doctor may choose another treatment if you wish to breast-feed, especially if the baby is a newborn or was born prematurely.

Driving and using machines

It is unlikely that Ifirmacombi will affect your ability to drive or use machinery. However, dizziness or fatigue may occasionally occur during treatment for high blood pressure. If this happens, talk to your doctor before driving or operating machinery.

Ifirmacombi contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to take Ifirmacombi

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Dosage of Ifirmacombi 150 mg/12.5 mg
The recommended dose of Ifirmacombi 150 mg/12.5 mg is one tablet daily. Your doctor will prescribe Ifirmacombi 150 mg/12.5 mg if your previous treatment has not sufficiently lowered your blood pressure. Your doctor will advise you on how to switch from your previous treatment to Ifirmacombi.
If this dose does not adequately lower your blood pressure, your doctor may prescribe Ifirmacombi 300 mg/12.5 mg.
Dosage of Ifirmacombi 300 mg/12.5 mg
The recommended dose of Ifirmacombi 300 mg/12.5 mg is one tablet daily.
Your doctor will prescribe Ifirmacombi 300 mg/12.5 mg if your previous treatment has not sufficiently lowered your blood pressure. Your doctor will advise you on how to switch from your previous treatment to Ifirmacombi.
If this dose does not adequately lower your blood pressure, your doctor may prescribe Ifirmacombi 300 mg/25 mg.
Dosage of Ifirmacombi 300 mg/25 mg
The recommended dose of Ifirmacombi 300 mg/25 mg is one tablet daily. This dose must not be increased.
Your doctor will prescribe Ifirmacombi 300 mg/25 mg if your previous treatment has not sufficiently lowered your blood pressure. Your doctor will advise you on how to switch from your previous treatment to Ifirmacombi.
If this dose does not adequately lower your blood pressure, your doctor will prescribe an additional treatment.
Method of administration
Ifirmacombi is for oral use. Swallow the tablets with sufficient liquid (for example, a glass of water). You may take Ifirmacombi with or without food. Try to take the medicine at the same time every day. It is important to continue the treatment unless otherwise instructed by your doctor.
Maximum blood pressure-lowering effect is achieved within 6–8 weeks after starting treatment.
If you take more Ifirmacombi than you should
If you accidentally take too many tablets, contact your doctor immediately.
Children must not take Ifirmacombi
Ifirmacombi must not be given to children under 18 years of age. If a child ingests any tablets, contact your doctor immediately.
If you forget to take Ifirmacombi
If you forget to take a dose, simply take your next dose at the usual time. Do not take a double dose to make up for the forgotten dose.
If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Some of these effects may be serious and may require medical intervention.
In patients treated with Irbesartan, rare cases of allergic skin reactions (rash, urticaria) as well as localized swelling of the face, lips and/or tongue have been reported.
If you experience any of the above symptoms or have difficulty breathing, stop taking Ifirmacombi and contact your doctor immediately.
The frequency of the side effects listed below is defined using the following convention:
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Very rare: may affect up to 1 in 10,000 people

The side effects reported in clinical studies in patients treated with Ifirmacombi were:

Common side effects (may affect up to 1 in 10 people)

• Nausea/vomiting
• Urinary disorders
• Fatigue
• Dizziness (also when moving from a sitting or lying position to a standing position)
• Blood tests may show increased levels of an enzyme that measures muscle and heart function (creatine kinase) or increased levels of substances that measure kidney function (azotemia, creatinine)

Inform your doctor if any of these side effects cause you problems.

Uncommon side effects (may affect up to 1 in 100 people)

• Diarrhea
• Hypotension
• Weakness
• Rapid heartbeat
• Hot flushes
• Swelling
• Sexual dysfunction (problems during sexual activity)
• Blood tests may show decreased levels of potassium and sodium in the blood.

Inform your doctor if any of these side effects cause you problems.

Side effects reported after the marketing of irbesartan and hydrochlorothiazide
Since the marketing of Ifirmacombi, some side effects have been reported. The frequency of these side effects is not known:

• Headache
• Tinnitus
• Cough
• Taste disturbances
• Indigestion
• Joint and muscle pain
• Impaired liver and kidney function
• Elevated potassium levels in the blood
• Allergic reactions such as rash, urticaria, localized swelling of the face, lips, mouth, tongue or throat
• Uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been reported. As with 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, severe allergic reactions (anaphylactic shock), reduced number of red blood cells (anaemia - symptoms may include fatigue, headache, shortness of breath during exercise, dizziness and pale appearance), reduced number of platelets (blood cells essential for blood clotting) and low blood sugar levels have also been reported.

Side effects associated with hydrochlorothiazide alone
Skin and lip cancer (non-melanoma skin cancer), loss of appetite; stomach irritation; stomach cramps, constipation; jaundice (yellowing of the skin and/or whites of the eyes); inflammation of the pancreas characterized by severe pain in the upper abdomen, often accompanied by nausea and vomiting; sleep disturbances; depression; blurred vision; reduced vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma); absence of white blood cells, which may lead to frequent infections and fever; reduced number of platelets (essential component for blood clotting), reduced number of red blood cells (anaemia) characterized by fatigue, headache, shortness of breath during physical exertion, dizziness and pale appearance; kidney problems; lung problems including pneumonia or fluid accumulation in the lungs; increased sensitivity of the skin to sunlight; inflammation of blood vessels; a skin disorder characterized by skin peeling over the entire body; lupus erythematosus, identified by a rash that may appear on the face, neck and scalp; allergic reactions; muscle weakness and cramps; altered heartbeat; drop in blood pressure upon changing body position; swelling of the salivary glands; elevated blood sugar levels; sugar in urine, increased levels of certain types of fat in the blood, elevated levels of uric acid in the blood which may cause gout.

Very rare side effects (may affect up to 1 in 10,000 people)
Acute breathing difficulty (signs include severe shortness of breath, fever, weakness and confusion). It is known that side effects associated with hydrochlorothiazide may increase with higher doses of hydrochlorothiazide.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ifirmacombi

Keep this medicine out of the sight and reach of children.
Do not use Ifirmacombi after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ifirmacombi contains

• The active substances are: irbesartan and hydrochlorothiazide.
  Ifirmacombi 150 mg/12.5 mg: Each film-coated tablet contains 150 mg of irbesartan (as irbesartan hydrochloride) and 12.5 mg of hydrochlorothiazide.
  Ifirmacombi 300 mg/12.5 mg: Each film-coated tablet contains 300 mg of irbesartan (as irbesartan hydrochloride) and 12.5 mg of hydrochlorothiazide.
  Ifirmacombi 300 mg/25 mg: Each film-coated tablet contains 300 mg of irbesartan (as irbesartan hydrochloride) and 25 mg of hydrochlorothiazide.

• The excipients 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, macrogol, talc, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) in the tablet coating. See section 2 “Ifirmacombi contains sodium”.
  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, macrogol, talc, titanium dioxide (E171) in the tablet coating. See section 2 “Ifirmacombi contains sodium”.
  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, macrogol, talc, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) in the tablet coating. See section 2 “Ifirmacombi contains sodium”.

Description of the appearance of Ifirmacombi and contents of the pack
Ifirmacombi 150 mg/12.5 mg
Pale pink, biconvex, oval film-coated tablets.
Ifirmacombi 300 mg/12.5 mg
White, biconvex, capsule-shaped film-coated tablets.
Ifirmacombi 300 mg/25 mg
Pale pink, biconvex, oval film-coated tablets.

Available pack sizes in blisters: 14, 28, 30, 56, 56 x1, 84, 90 and 98 film-coated tablets. Not all pack sizes may be marketed.

Marketing Authorization Holder
KRKA, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto, Slovenia

Responsible for batch release
KRKA, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto
Slovenia

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

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien
KRKA Belgium, S.A.
Tél/Tel: +32 (0) 487 50 73 62

България (Bulgaria)
КРКА България ЕООД
Teл.: +359 (02) 962 34 50

Česká republika (Czech Republic)
KRKA ČR, s.r.o.
Tel: +420 (0) 221 115 150

Danmark (Denmark)
KRKA Sverige AB
Tlf: +46 (0)8 643 67 66 (SE)

Deutschland (Germany)
TAD Pharma GmbH
Tel: +49 (0) 4721 606-0

Eesti (Estonia)
KRKA, d.d., Novo mesto – Eesti filiaal
Tel: +372 (0) 6 671 658

Ελλάδα (Greece)
KRKA ΕΛΛΑΣ ΕΠΕ
Τηλ: +30 2100101613

España (Spain)
KRKA Farmacéutica, S.L.
Tel: +34 911 61 03 80

France
KRKA France Eurl
Tél: +33 (0)1 57 40 82 25

Hrvatska (Croatia)
KRKA - FARMA d.o.o.
Tel: +385 1 6312 100

Ireland
KRKA Pharma Dublin, Ltd.
Tel: +353 1 413 3710

Ísland (Iceland)
LYFIS ehf.
Sími: +354 534 3500

Italia (Italy)
KRKA Farmaceutici Milano S.r.l.
Tel: +39 02 3300 8841

Κύπρος (Cyprus)
KI.PA. (PHARMACAL) LIMITED
Τηλ: +357 24 651 882

Latvija (Latvia)
KRKA Latvija SIA
Tel: +371 6 733 86 10

Lietuva (Lithuania)
UAB KRKA Lietuva
Tel: +370 5 236 27 40

Luxembourg/Luxemburg
KRKA Belgium, S.A.
Tél/Tel: +32 (0) 487 50 73 62 (BE)

Magyarország (Hungary)
KRKA Magyarország Kereskedelmi Kft.
Tel.: +36 (1) 355 8490

Malta
E. J. Busuttil Ltd.
Tel: +356 21 445 885

Nederland (Netherlands)
KRKA Belgium, S.A.
Tel: +32 (0) 487 50 73 62 (BE)

Norge (Norway)
KRKA Sverige AB
Tlf: +46 (0)8 643 67 66 (SE)

Österreich (Austria)
KRKA Pharma GmbH, Wien
Tel: +43 (0)1 66 24 300

Polska (Poland)
KRKA-POLSKA Sp. z o.o.
Tel.: +48 (0)22 573 7500

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: +351 (0)21 46 43 650

România (Romania)
KRKA Romania S.R.L., Bucharest
Tel: +4 021 310 66 05

Slovenija (Slovenia)
KRKA, d.d., Novo mesto
Tel: +386 (0) 1 47 51 100

Slovenská republika (Slovakia)
KRKA Slovensko, s.r.o.
Tel: +421 (0) 2 571 04 501

Suomi/Finland
KRKA Finland Oy
Puh/Tel: +358 20 754 5330

Sverige (Sweden)
KRKA Sverige AB
Tel: +46 (0)8 643 67 66 (SE)

United Kingdom (Northern Ireland)
KRKA Pharma Dublin, Ltd
Tel: +353 1 413 3710

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/