IFIRMACOMBI 300 mg/12.5 mg FILM-COATED TABLETS

2. What you need to know before you take Ifirmacombi

Do not take Ifirmacombi

• if you are allergicto irbesartan or any of the other ingredients of this medicine (listed in section 6)
• if you are allergicto hydrochlorothiazide or to any other sulfonamide-derived medication
• if you are more than 3 months pregnant. (In any case, it is recommended to avoid taking Ifirmacombi at the start of pregnancy – see section Pregnancy)
• if you have severe liver or kidney problems
• if you have difficulty urinating
• if your doctor detects that you have persistently high levels of calcium or low levels of potassium in your blood
• if you have diabetes or kidney insufficiency and are being treated with a blood pressure-lowering medicine that contains aliskiren

Warnings and precautions

Consult your doctorbefore starting to take Ifirmacombi and in any of the following cases:

• if you have excessive vomiting or diarrhea
• if you have kidney problemsor if you have had a kidney transplant
• if you have heart problems
• if you have liver problems
• if you have diabetes
• if you have systemic lupus erythematosus(also known as lupus or SLE)
• if you have primary aldosteronism(a condition related to excessive production of the hormone aldosterone, leading to sodium retention and increased blood pressure)
• If you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, in particular its long-term use at high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Ifirmacombi.
• if you are taking any of the following medicines used to treat high blood pressure:
• an angiotensin-converting enzyme inhibitor (ACE inhibitor) (e.g., enalapril, lisinopril, ramipril), particularly 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 information under the heading “Do not take Ifirmacombi”.

If you are pregnant, think you may be pregnant, or are planning to become pregnant, inform your doctor. Ifirmacombi is not recommended during pregnancy and must not be taken after the third month of pregnancy as it may cause serious harm to your baby (see section Pregnancy).

You must also inform your doctor:

• if you are on a low-salt diet
• if you experience any of the following symptoms: feeling of thirst, dry mouth, generalized weakness, feeling of sleepiness, muscle pain or cramps, nausea, vomiting,or rapid heartbeat, as they may indicate an excessive effect of hydrochlorothiazide (contained in Ifirmacombi)
• if you experience an increased sensitivity of your skin to the sunwith symptoms of sunburn (such as redness, itching, swelling, blisters) that occurs more quickly than usual
• if you are going to have surgery(surgical intervention) or if you are going to be given anesthetics.
• if you experience changes in your vision or pain in one or both eyeswhile taking Ifirmacombi. This could be a sign of glaucoma, increased pressure in your eyes. You should stop taking Ifirmacombi and seek medical attention.

Hydrochlorothiazide contained in this medicine may cause positive results in doping tests.

Children and adolescents

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

Using Ifirmacombi with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Diuretics, such as hydrochlorothiazide contained in Ifirmacombi, may have an effect on other medicines. Do not take preparations containing lithium with Ifirmacombi without your doctor's supervision.

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

• If you are taking an angiotensin-converting enzyme inhibitor (ACE inhibitor) or aliskiren (see also the information under the headings “Do not take Ifirmacombi” and “Warnings and precautions”).

You may need to have blood tests if you take:

• potassium supplements
• salt substitutes that contain potassium
• potassium-sparing diuretics or other diuretics (tablets that increase urine production)
• certain laxatives
• medicines used to treat gout
• vitamin D supplements
• medicines to control heart rhythm
• medicines for diabetes (oral agents or insulins)
• carbamazepine (a medicine for the treatment of epilepsy)

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

Taking Ifirmacombi with food, drinks, and alcohol

Ifirmacombi can be taken with or without food.

Due to the hydrochlorothiazide contained in Ifirmacombi, if you drink alcohol while being treated with this medicine, you may have a greater feeling of dizziness when standing up, especially when getting up from a sitting position.

Pregnancy, breastfeeding, and fertility

Pregnancy

You should inform your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant. Your doctor will normally advise you to stop taking Ifirmacombi before you become pregnant or as soon as you find out you are pregnant and will recommend that you take another blood pressure-lowering medicine instead. Ifirmacombi is not recommended during pregnancy and must not be taken after the third month of pregnancy as it may cause serious harm to your baby.

Breastfeeding

Inform your doctor if you are about to start or are breastfeeding, as Ifirmacombi is not recommended for use during breastfeeding. Your doctor may decide to give you a different treatment that is more suitable if you want to breastfeed, especially if you are breastfeeding a newborn or premature baby.

Driving and using machines

Ifirmacombi is unlikely to affect your ability to drive or use machines.

However, during treatment for high blood pressure, dizziness or fatigue may occasionally occur. If you experience these symptoms, talk to your doctor before driving or using machines.

Ifirmacombi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially “sodium-free”.

3. How to take Ifirmacombi

Follow exactly the instructions of your doctor for taking this medicine. If you are unsure, consult your doctor or pharmacist again.

Dose of Ifirmacombi 150 mg/12.5 mg

The recommended dose of Ifirmacombi 150 mg/12.5 mg is one tablet per day. In general, your doctor will prescribe Ifirmacombi 150 mg/12.5 mg when previous treatments you received did not sufficiently reduce your blood pressure. Your doctor will indicate how to switch from previous treatments to Ifirmacombi.

If this dose does not help reduce your blood pressure sufficiently, your doctor may prescribe Ifirmacombi 300 mg/12.5 mg.

Dose of Ifirmacombi 300 mg/12.5 mg

The recommended dose of Ifirmacombi 300 mg/12.5 mg is one tablet per day. In general, your doctor will prescribe Ifirmacombi 300 mg/12.5 mg when previous treatments you received did not sufficiently reduce your blood pressure. Your doctor will indicate how to switch from previous treatments to Ifirmacombi.

If this dose does not help reduce your blood pressure sufficiently, your doctor may prescribe Ifirmacombi 300 mg/25 mg.

Dose of Ifirmacombi 300 mg/25 mg

The recommended dose of Ifirmacombi 300 mg/25 mg is one tablet per day. This dose should not be increased. In general, your doctor will prescribe Ifirmacombi 300 mg/25 mg when previous treatments you received did not sufficiently reduce your blood pressure. Your doctor will indicate how to switch from previous treatments to Ifirmacombi.

If this medicine does not help reduce your blood pressure sufficiently, your doctor may prescribe additional treatment.

Method of administration

Ifirmacombi is taken orally. The tablets should be swallowed with a sufficient amount of liquid (e.g., a glass of water). You can take Ifirmacombi with or without food. Try to take your daily dose at the same time each day. It is important that you continue taking Ifirmacombi until your doctor advises you to stop.

The maximum blood pressure-lowering effect should be 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 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 dose, simply take your normal dose when it is due next. Do not take a double dose to make up for forgotten doses.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some of these effects can be serious and may require medical attention.

Rarely, cases of allergic skin reactions (skin rash, urticaria) have been reported in patients treated with irbesartan, as well as localized swelling in the face, lips, and/or tongue. If you have any of the above symptoms or experience shortness of breath, stop taking Ifirmacombi and contact your doctor immediately.

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

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

• nausea/vomiting,
• urination anomalies,
• fatigue
• dizziness (including dizziness when standing up from a lying or sitting position)
• blood tests may show elevated levels of an enzyme that measures muscle and heart function (creatine kinase) or elevated levels of substances that measure kidney function (urea, creatinine).

If any of these side effects bother you, talk to your doctor.

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

• diarrhea,
• low blood pressure,
• fainting,
• rapid heartbeat,
• flushing,
• fluid retention (edema)
• sexual dysfunction (sexual function disorders).
• blood tests may show low levels of sodium and potassium in your blood.

If any of these side effects bother you, talk to your doctor.

Side effects reported since the marketing of the irbesartan and hydrochlorothiazide combination

Since the marketing of Ifirmacombi, some side effects have been reported. The side effects with frequency not known are:

• headache,
• ringing in the ears,
• cough,
• taste disturbance,
• indigestion,
• joint and muscle pain,
• liver function disorders and kidney failure,
• high levels of potassium in your blood and
• allergic reactions such as skin rash, urticaria, swelling of the face, lips, mouth, tongue, or throat
• cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been observed.

As with all combinations of two active substances, it cannot be excluded that side effects associated with each of the components may occur.

Side effects associated only with irbesartan

In addition to the side effects described above, chest pain, severe allergic reactions (anaphylactic shock), and a decrease in the number of platelets (a blood cell essential for blood clotting) have also been observed.

Side effects associated with hydrochlorothiazide in monotherapy:

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); pancreatitis characterized by severe upper stomach pain, often with nausea and vomiting; sleep disorders; depression; blurred vision; low white blood cell count, which can lead to frequent infections, fever; decreased platelet count (a blood cell essential for blood clotting), decreased red blood cell count (anemia) characterized by fatigue, headaches, shortness of breath when exercising, dizziness, and paleness; kidney disease; lung disorders including pneumonia or fluid accumulation in the lungs; increased sensitivity of the skin to the sun; blood vessel inflammation; a skin disease characterized by peeling of the skin all over the body; cutaneous lupus erythematosus, which is identified by a rash that can appear on the face, neck, and scalp; allergic reactions; weakness and muscle spasms; heart rhythm disturbances; low blood pressure after changing body position; swelling of the salivary glands; high blood sugar levels; sugar in the urine; increased levels of certain blood fats; high levels of uric acid in the blood, which can cause gout.

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible that the side effects are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Ifirmacombi

Keep this medicine out of the sight and reach of children.

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

No special storage conditions are required.

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

6. Packaging Content and Additional Information

Ifirmacombi Composition

• The active ingredients are irbesartan and hydrochlorothiazide.

Each Ifirmacombi 150 mg/12.5 mg film-coated tablet contains 150 mg of irbesartan (as irbesartan hydrochloride) and 12.5 mg of hydrochlorothiazide.

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

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

• The other ingredients of Ifirmacombi 150 mg/12.5 mg are: mannitol, hydroxypropyl cellulose, hydroxypropyl cellulose of low substitution, sodium starch glycolate, talc, macrogol 6000, and 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. See section 2 "Ifirmacombi contains sodium".
• The other ingredients of Ifirmacombi 300 mg/12.5 mg are: mannitol, hydroxypropyl cellulose, hydroxypropyl cellulose of low substitution, sodium starch glycolate, talc, macrogol 6000, and hydrogenated castor oil in the tablet core, and polyvinyl alcohol, titanium dioxide (E171), macrogol, and talc in the film coating. See section 2 "Ifirmacombi contains sodium".
• The other ingredients of Ifirmacombi 300 mg/25 mg are: mannitol, hydroxypropyl cellulose, hydroxypropyl cellulose of low substitution, sodium starch glycolate, talc, macrogol 6000, and 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. See section 2 "Ifirmacombi contains sodium".

Appearance of Ifirmacombi and Packaging Content

Ifirmacombi 150 mg/12.5 mg

Film-coated tablet (tablet) is pale pink, biconvex, and oval.

Ifirmacombi 300 mg/12.5 mg

Film-coated tablet (tablet) is white, biconvex, and capsule-shaped.

Ifirmacombi 300 mg/25 mg

Film-coated tablet (tablet) is pale pink, biconvex, and capsule-shaped.

Ifirmacombi film-coated tablets are available in blister packs of 14, 28, 30, 56, 56x1, 84, 90, and 98 film-coated tablets.

Only some pack sizes may be marketed.

Marketing Authorisation Holder

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer

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 about this medicinal product, please contact the local representative of the marketing authorisation holder:

Date of Last Revision of this Leaflet:

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