Package Leaflet: Information for the User

Ifirmacombi 150 mg/12.5 mg Film-Coated Tablets

Ifirmacombi 300 mg/12.5 mg Film-Coated Tablets

Ifirmacombi 300 mg/25 mg Film-Coated Tablets

Irbesartan/Hydrochlorothiazide

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as 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 others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4

Ifirmacombi is an association of two active principles, irbesartan and hydrochlorothiazide.

Irbesartan belongs to a group of medications known as angiotensin-II receptor antagonists.

Angiotensin-II is a substance produced in the body that binds to blood vessel receptors, causing them to contract. This results in an increase in blood pressure. Irbesartan prevents the binding of angiotensin-II to these receptors, relaxing blood vessels and reducing blood pressure.

Hydrochlorothiazide belongs to a group of medications (called thiazide diuretics) that increase the amount of urine eliminated, reducing blood pressure.

The two active principles of Ifirmacombi act together to achieve a reduction in blood pressure greater than that obtained with each one separately.

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

Do not take Ifirmacombi

• if you areallergicto irbesartan, or to any of the other components of this medication (listed in section 6)
• if you areallergicto hydrochlorothiazide or to any other medication derived from sulfonamides
• if you aremore than 3 months pregnant. (In any case, it is better to avoid taking Ifirmacombi at the beginning of your pregnancy – see Pregnancy section)
• if you havesevere liver or kidney problems
• if you havedifficulty urinating
• if your doctor detects that you havepersistently elevated calcium levels or low potassium levels in your blood
• if you have diabetes or kidney insufficiency and are being treated with a medication to lower blood pressure that contains aliskiren

Warnings and precautions

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

• if you haveexcessive vomiting or diarrhea
• if you havekidney problemsor if you have had akidney transplant
• if you haveheart problems
• if you haveliver problems
• if you havediabetess
• if you havelupus erythematosus(also known as lupus or LES)
• if you haveprimary aldosteronism(a condition related to the excessive production of the hormone aldosterone, which causes sodium retention and, in turn, an increase in blood pressure)
• If you have had skin cancer or if a skin lesion appears unexpectedly during treatment. The treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin cancer 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 medications used to treat high blood pressure (hypertension):
• a converting enzyme inhibitor (ACEI) (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 electrolyte levels (e.g. potassium) at regular intervals.

See also the information under the heading “Do not take Ifirmacombi”.

If you are pregnant, if you suspect you may be pregnantor if you plan to become pregnant, you must inform your doctor. Ifirmacombi is not recommended for use at the beginning of pregnancy (first 3 months), and in no case should it be administered after the third month of pregnancy because it may cause serious harm to your baby (see Pregnancy section).

You must also inform your doctor:

• if you are following alow-sodium diet
• if you experience any of the following symptoms:thirst, dry mouth, generalized weakness, drowsiness, muscle pain or cramps, nausea, vomiting,orrapid heartbeat, as they may indicate excessive hydrochlorothiazide effect (contained in Ifirmacombi)
• if you experience an increase insensitivity to the sunwith symptoms of sunburn (such as redness, itching, swelling, blisters) that occur more quickly than usual
• ifyou are to undergo surgery(surgical intervention) or ifyou are to receive anesthetics.
• if you experiencechanges in your vision or eye painwhile taking Ifirmacombi. This may be a sign of glaucoma development, increased eye pressure. You should discontinue Ifirmacombi treatment and seek medical attention.

The hydrochlorothiazide contained in this medication may cause positive results in doping control.

Children and adolescents

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

Use of Ifirmacombi with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Diuretics, such as hydrochlorothiazide contained in Ifirmacombi, may affect other medications. Do not take with Ifirmacombi preparations containing lithium without your doctor's supervision.

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

• if you are taking an ACEI 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
• sodium-free salt substitutes containing potassium
• potassium-sparing diuretics (tablets that increase urine production)
• some laxatives
• medications used to treat gout
• vitamin D supplements
• medications for heart rhythm control
• diabetes medications (oral agents or insulin)
• carbamazepine (a medication for epilepsy treatment)

You should also inform your doctor if you are taking other medications to lower your blood pressure, steroids, and medications for cancer, analgesics, medications 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 taking this medication, you may experience a greater sense of dizziness when standing up, especially when getting up from a seated position.

Pregnancy, breastfeeding, and fertility

Pregnancy

You must inform your doctor if you are pregnant, if you suspect you may be pregnantor if you plan to become pregnant. Your doctor will usually advise you to stop taking Ifirmacombi before becoming pregnant or as soon as you become pregnant and recommend taking another antihypertensive medication instead. Ifirmacombi is not recommended for use during pregnancy and should not be administered after the third month of pregnancy because it may cause serious harm to your baby when administered from that point on.

Breastfeeding

Inform your doctor if you plan to start or are breastfeeding, as Ifirmacombi is not recommended for use during this period. Your doctor may decide to administer a more suitable treatment if you want to breastfeed, especially for newborns or premature babies.

Driving and operating machinery

It is unlikely that Ifirmacombi will affect your ability to drive vehicles or operate machinery.

However, during hypertension treatment, you may occasionally experience dizziness or fatigue. If you experience these symptoms, talk to your doctor before driving or operating machinery.

Ifirmacombi contains sodium

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Dosage of Ifirmacombi 150 mg/12.5 mg

The recommended dosage 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 dosage does not help sufficiently reduce your blood pressure, your doctor may prescribe Ifirmacombi 300 mg/12.5 mg.

Dosage of Ifirmacombi 300 mg/12.5 mg

The recommended dosage 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 dosage does not help sufficiently reduce your blood pressure, your doctor may prescribe Ifirmacombi 300 mg/25 mg.

Dosage of Ifirmacombi 300 mg/25 mg

The recommended dosage of Ifirmacombi 300 mg/25 mg is one tablet per day. This dosage 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 medication does not help sufficiently reduce your blood pressure, your doctor may prescribe additional treatment.

Administration form

Ifirmacombi is administered orally. 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 every day. It is essential that you continue taking Ifirmacombi until your doctor advises you otherwise.

The maximum blood pressure-reducing 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 forget to take a dose, simply take your regular dose when it is due next. Do not take a double dose to compensate for the missed doses.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

In rare cases, cases of skin allergic reactions (skin rash, urticaria) have been reported in patients treated with irbesartan, as well as localized inflammation in the face, lips, and/or tongue.If you have any of the previous 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:

Frequent side effects(may affect up to 1 in 10 patients):

• nausea/vomiting,
• urination abnormalities,
• fatigue
• dizziness (including that which occurs 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 nitrogen in the blood, creatinine).

If any of these side effects cause you problems,consult your doctor.

Rare side effects(may affect up to 1 in 100 patients):

• diarrhea,
• low blood pressure,
• syncope,
• tachycardia,
• flushing,
• swelling due to fluid retention (edema)
• sexual dysfunction (alterations in sexual function).
• blood tests may show low levels of sodium and potassium in your blood.

If any of these side effects cause you problems,consult your doctor.

Side effects since the marketing of the irbesartan and hydrochlorothiazide combination

Since the marketing of Ifrimacombi, some side effects have been reported. The side effects observed with unknown frequency are:

• headache,
• tinnitus in the ears,
• cough,
• alteration of taste,
• indigestion,
• joint and muscle pain,
• liver function alterations and kidney insufficiency,
• elevated levels of potassium in your blood and
• allergic reactions such as skin rash, urticaria, swelling of the face, lips, mouth, tongue, or throat
• also, rare cases of jaundice (yellowing of the skin and/or white of the eyes) have been observed.

As with all combinations of two active principles, the side effects associated with each component cannot be ruled out.

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 (an essential blood cell for blood coagulation) 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 white of the eyes); pancreatitis characterized by severe upper stomach pain, often with nausea and vomiting; sleep disorders; depression; blurred vision; lack of white blood cells, which can lead to frequent infections, fever; decrease in the number of platelets (essential blood cells for blood coagulation), decrease in the number of red blood cells (anemia) characterized by fatigue, headaches, shortness of breath during exercise, dizziness, and paleness; kidney disease; respiratory alterations including pneumonia or fluid accumulation in the lungs; increased skin sensitivity to the sun; inflammation of blood vessels; a skin disease characterized by peeling of the skin all over the body; cutaneous lupus erythematosus, identified by a rash that can appear on the face, neck, and scalp; allergic reactions; muscle weakness and spasms; alteration of heart rhythm; reduction of blood pressure after a change in body position; swelling of salivary glands; high levels of sugar in the blood; sugar in the urine; increases in some types of blood fats; high levels of uric acid in the blood, which can cause gout.

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after CAD/EXP. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Ifirmacombi

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

Ifirmacombi 150 mg/12.5 mg

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

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 with 14, 28, 30, 56, 56x1, 84, 90, and 98 film-coated tablets.

Only some package sizes may be marketed.

Marketing authorization holder

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

Responsible for manufacturing

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

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

For more information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu/.