Gaduar

Patient Information Leaflet

Gaduar 20 mg/5 mg/12.5 mg film-coated tablets, 40 mg/5 mg/12.5 mg film-coated tablets, 40 mg/5 mg/25 mg film-coated tablets, 40 mg/10 mg/12.5 mg film-coated tablets, 40 mg/10 mg/25 mg film-coated tablets

olmesartan medoxomil/amlodipine/hydrochlorothiazide
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• 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 others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Gaduar is and what it is used for
2. What you need to know before taking Gaduar
3. How to take Gaduar
4. Possible side effects
5. How to store Gaduar
6. Contents of the pack and other information

1. What Gaduar is and what it is used for

Gaduar contains three substances called olmesartan medoxomil, amlodipine (as amlodipine besilate), and hydrochlorothiazide. All three substances are used to control hypertension.

• Olmesartan medoxomil belongs to a group of medicines known as “angiotensin II receptor antagonists” which lower blood pressure by relaxing blood vessels.
• Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine also lowers blood pressure by relaxing blood vessels.
• Hydrochlorothiazide belongs to a group of substances called “thiazide diuretics” (medicines that stimulate diuresis). It lowers blood pressure by helping the body eliminate excess water, increasing urine production by the kidneys.

The combined action of these substances helps reduce blood pressure.
Gaduar is used to treat high blood pressure:

• in adult patients whose blood pressure is not adequately controlled by a fixed-dose combination of olmesartan medoxomil and amlodipine, or
• in patients already taking a fixed-dose combination of olmesartan medoxomil and hydrochlorothiazide plus amlodipine as a single tablet, or a fixed-dose combination of olmesartan medoxomil and amlodipine plus hydrochlorothiazide as a single tablet.

2. What you need to know before taking Gaduar

Do not take Gaduar if:

• you are allergic to olmesartan medoxomil, amlodipine, or a specific group of calcium antagonists (the dihydropyridines), to hydrochlorothiazide or substances similar to hydrochlorothiazide (called sulfonamides), or to any of the excipients of this medicine listed in section 6. If you think you may be allergic, speak with your doctor before taking Gaduar.
• you have severe kidney problems.
• you suffer from diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
• you have low levels of potassium or sodium, or high levels of calcium or uric acid (with symptoms of gout or kidney stones) in your blood that do not improve with treatment.
• you are more than three months pregnant (it is best to avoid taking Gaduar even in the early stages of pregnancy – see section “Pregnancy and breastfeeding”).
• you have severe liver problems, if bile secretion is impaired or bile flow is blocked (e.g. due to gallstones), or if you have jaundice (yellowing of the skin and eyes).
• you suffer from reduced blood flow to tissues, with symptoms such as low blood pressure, weak pulse, rapid heartbeat, or shock (including cardiogenic shock, meaning shock due to severe heart problems).
• you have very low blood pressure.
• blood flow from your heart is slow or obstructed. This occurs if the blood vessels or valves carrying blood out of the heart are narrowed (aortic stenosis).
• you have reduced cardiac output due to a heart attack (acute myocardial infarction). Reduced cardiac output manifests as difficulty breathing or swelling of the feet and ankles.

If you think you are in any of the above conditions, do not take Gaduar.

Warnings and precautions

Talk to your doctor or pharmacist before taking Gaduar.

Consult your doctor if you are taking any of the following medicines used to treat high blood pressure:

• an 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 levels of electrolytes (e.g. potassium) in your blood at regular intervals.

See also the section “Do not take Gaduar if:”

Inform your doctor if you also have any of the following health conditions:

• Kidney problems or kidney transplant.
• Liver disease.
• Heart failure or problems with heart valves or heart muscle.
• Severe vomiting, diarrhea, treatment with high doses of diuretics, or if you are on a low-salt diet.
• Elevated potassium levels in the blood.
• Problems with the adrenal glands (hormone-producing glands located above the kidneys).
• Diabetes.
• Lupus erythematosus (an autoimmune disease).
• Allergies or asthma.
• Skin reactions such as sunburn or rash after exposure to sunlight or sunlamps.
• if you have previously had skin cancer or are developing an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use with high doses, may increase the risk of certain types of skin cancer and

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cancer of the lips (non-melanoma skin cancer). Protect your skin from exposure to sunlight and
UV radiation while taking Gaduar.

• If you experience vision loss or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye and may occur within a few hours to weeks after taking Gaduar. Increased eye pressure, if untreated, can lead to permanent vision damage. If you have previously had an allergy to penicillins or sulfonamides, you are at higher risk of developing this effect. Inform your doctor if any of the following symptoms occur:
• severe and prolonged diarrhea with significant weight loss. Your doctor will evaluate your symptoms and decide whether to continue this antihypertensive treatment.

As with any medicine that lowers blood pressure, excessive reduction in blood pressure in patients with circulatory disorders of the heart or brain may lead to a heart attack or stroke. Your doctor will therefore carefully monitor your blood pressure.

Gaduar may cause increased levels of fats and uric acid (a cause of gout – painful joint swelling) in the blood. Your doctor may want to perform periodic blood tests to monitor these conditions.

Levels of certain substances called electrolytes in the blood may change. Your doctor may want to perform periodic blood tests to monitor these conditions. Signs of electrolyte imbalance include: thirst, dry mouth, muscle pain or cramps, muscle weakness, low blood pressure (hypotension), feeling weak, lethargic, tired, drowsy or unrested, nausea, vomiting, reduced need to urinate, rapid heartbeat. Inform your doctor if these symptoms occur.

If you are scheduled for parathyroid function tests, stop taking Gaduar before the tests are performed.

You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Gaduar is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the baby if taken during this period (see section “Pregnancy and breastfeeding”).

Children and adolescents (up to 18 years)

Gaduar is not recommended for children and adolescents under 18 years of age.

Important information for athletes

Using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Gaduar

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any of the following medicines:

• Other medicines that lower blood pressure, as they may enhance the effect of Gaduar. Your doctor may need to adjust the dose and/or take other precautions: if you are taking an ACE inhibitor or aliskiren (see also the sections “Do not take Gaduar if” and “Warnings and precautions”).
• Lithium (a medicine used to treat mood swings and certain types of depression) taken together with Gaduar may increase lithium toxicity. If you need to take lithium, your doctor will monitor lithium levels in your blood.
• Diltiazem, verapamil, medicines used for heart rhythm problems and high blood pressure.

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• Rifampicin, erythromycin, clarithromycin, tetracyclines, or sparfloxacin, antibiotics used for tuberculosis and other infections.
• St. John’s wort (Hypericum perforatum), a herbal remedy for depression.
• Cisapride, used to speed up food transit through the stomach and intestines.
• Difemanil, used to treat slow heartbeat or reduce sweating.
• Halofantrine, used for malaria.
• Vincamine i.v., used to improve circulation in the nervous system.
• Amantadine, used for Parkinson’s disease.
• Potassium supplements, potassium-containing salt substitutes, diuretics, or heparin (to thin the blood and prevent thrombosis), ACE inhibitors (to lower blood pressure), laxatives, steroids, adrenocorticotropic hormone (ACTH), carbenoxolone (a medicine used to treat mouth and stomach ulcers), sodium penicillin G (also known as benzylpenicillin sodium, an antibiotic), certain painkillers such as acetylsalicylic acid (aspirin) or salicylates. Taking these medicines together with Gaduar may alter potassium levels in the blood.
• Non-steroidal anti-inflammatory drugs (NSAIDs, medicines used to reduce pain, swelling, and other symptoms of inflammation, including arthritis) taken together with Gaduar may increase the risk of kidney failure. The effectiveness of Gaduar may be reduced by NSAIDs. When high doses of salicylates are taken, central nervous system toxic effects may be increased.
• Sleeping pills, sedatives, and antidepressants, taken together with Gaduar may cause a sudden drop in blood pressure when standing up.
• Colesevelam hydrochloride, a medicine that reduces cholesterol levels in the blood, which may reduce the effect of Gaduar. Your doctor may advise you to take Gaduar at least 4 hours before colesevelam hydrochloride.
• Some antacids (used for indigestion or stomach acidity) may slightly reduce the effectiveness of Gaduar.
• Some muscle relaxants, such as baclofen and tubocurarine.
• Anticholinergic medicines, such as atropine and biperiden.
• Calcium supplements.
• Dantrolene (infusion for severe body temperature alterations).
• Simvastatin, a substance used to reduce cholesterol and fat (triglyceride) levels in the blood.
• Medicines used to control your body’s immune response (such as tacrolimus, cyclosporine) that allow your body to accept transplanted organs.

In addition, inform your doctor or pharmacist if you are taking, have recently taken, or might take any of the following medicines for:

• Treating certain mental disorders such as thioridazine, chlorpromazine, evopromazine, trifluoperazine, ciamemazine, sulpiride, amisulpride, pimozide, sultopride, tiapride, droperidol, or haloperidol.
• Treating hypoglycemia (e.g. diazoxide) or hypertension (beta-blockers, methyldopa), as Gaduar may affect the action of these medicines.
• Treating heart rhythm disorders such as mizolastine, pentamidine, terfenadine, dofetilide, ibutilide, or injectable erythromycin.
• Treating HIV/AIDS (e.g. ritonavir, indinavir, nelfinavir).
• Treating fungal infections (e.g. ketoconazole, itraconazole, amphotericin).
• Treating heart conditions such as quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, bepridil, or digitalis.
• Treating tumors such as amifostine, cyclophosphamide, or methotrexate.
• Increasing blood pressure and slowing heart rate such as noradrenaline.
• Treating gout such as probenecid, sulfinpyrazone, and allopurinol.
• Reducing plasma fat levels such as cholestyramine and colestipol.
• Reducing plasma glucose levels such as metformin or insulin.

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Inform your doctor or pharmacist if you are taking, have recently taken, or plan to take any other
medicine.

Gaduar with food, drinks, and alcohol

Gaduar may be taken with or without food.

People taking Gaduar must not consume grapefruit or grapefruit juice, as grapefruit and its juice may increase blood levels of the active substance amlodipine, which could lead to an unpredictable increase in the hypotensive effect of Gaduar.

Be cautious when drinking alcohol while taking Gaduar, as some individuals may experience fainting or dizziness. If this happens to you, do not drink alcohol.

Elderly

If you are over 65 years old, your doctor will regularly monitor your blood pressure with each dose increase to avoid excessive lowering.

Pregnancy and breastfeeding

Pregnancy

You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Normally, your doctor will advise you to stop taking Gaduar before becoming pregnant or as soon as you find out you are pregnant, and will recommend an alternative medicine to Gaduar. Gaduar is not recommended during pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the baby if taken after the third month of pregnancy.

If you become pregnant while taking Gaduar, inform your doctor immediately and seek medical advice.

Breastfeeding

Inform your doctor if you are breastfeeding or planning to breastfeed. It has been shown that amlodipine and hydrochlorothiazide pass into breast milk in small amounts. Gaduar is not recommended for women who are breastfeeding, and your doctor may choose an alternative treatment if you wish to breastfeed.

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Driving and use of machines

You may experience drowsiness, discomfort, dizziness, or headache during treatment for high blood pressure. If this occurs, do not drive or operate machinery until symptoms resolve. Consult your doctor for advice.

Gaduar contains lactose

If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Gaduar

Take this medicine exactly as your doctor or pharmacist has told you. If
you have any doubts, consult your doctor or pharmacist.

• The recommended dose of Gaduar is one tablet daily.

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• The tablet can be taken with or without food. Swallow the tablet with some liquid (such as a glass of water). Do not chew the tablets. Do not take it with grapefruit juice.
• If possible, take your daily dose at the same time each day, for example with breakfast.

If you take more Gaduar than you should
If you take more tablets than you should, you may experience a drop in blood pressure with symptoms
such as dizziness, or increased or decreased heart rate.
If you take more tablets than prescribed or if a child accidentally swallows any, go immediately to your doctor or the nearest emergency department, taking the medicine pack or this leaflet with you.
If you forget to take Gaduar
If you forget to take a dose, take your usual dose the next day. Do not take a double dose to make up for the missed dose.
If you stop taking Gaduar
It is important to continue taking Gaduar unless your doctor tells you to stop.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. If they occur, they are mostly mild and do not require discontinuation of treatment.

Although they do not occur in all individuals, the following two side effects can be serious:

Allergic reactions with swelling of the face, mouth and/or larynx (site of the vocal cords), associated with itching and skin rash, may occur during treatment with this medicine. If this happens, stop taking Gaduar and contact your doctor immediately.

Gaduar may cause excessive lowering of blood pressure in sensitive individuals, which could lead to severe dizziness or fainting. If this happens, stop taking Gaduar, contact your doctor immediately, and remain lying down.

Gaduar is a combination of three active substances. The information below first lists other side effects reported so far with the combination olmesartan medoxomil/amlodipine/hydrochlorothiazide (in addition to those already mentioned above), followed by side effects known for each of the three substances when taken alone or when two substances are administered together.

To give you an idea of how many patients have experienced these side effects, they are categorized as common, uncommon, rare, and very rare.

These are the other side effects with the combination olmesartan medoxomil/amlodipine/hydrochlorothiazide:

If they occur, they are mostly mild and do not require discontinuation of treatment.

Common
(may affect up to 1 in 10 people)
Upper respiratory tract infection; inflammation of the throat and nose; urinary tract infection; dizziness; headache; awareness of heartbeat; low blood pressure; nausea; diarrhoea; constipation; cramps; joint swelling; urgency to urinate; weakness; swelling of the ankles; fatigue; laboratory test abnormalities.

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Uncommon
(may affect up to 1 in 100 people)
Dizziness upon standing; vertigo; rapid heartbeat; feeling of weakness; facial flushing and sensation of warmth; cough; dry mouth; muscle weakness; inability to achieve or maintain erection.

These are the side effects known for each of the components taken alone or for two components taken together:

These may be side effects of Gaduar even though they have not been observed so far with this medicine.

Very common
(may affect more than 1 in 10 people)
Edema (fluid retention).

Common
(may affect up to 1 in 10 people)
Bronchitis; gastric and intestinal infection; vomiting; increased blood glucose; glucose in urine; confusion; drowsiness; visual disturbances (including double and blurred vision); runny or stuffy nose; throat inflammation; breathing difficulty; cough; abdominal pain; heartburn; gastric discomfort; flatulence; joint or bone pain; back pain; skeletal pain; blood in urine; influenza-like symptoms; chest pain; pain.

Uncommon
(may affect up to 1 in 100 people)
Reduction in a type of blood cell called platelets, which may cause easy bruising or prolonged bleeding time; anaphylactic reactions; abnormal decrease in appetite (anorexia); difficulty falling asleep; irritability; mood changes including anxiety; feeling of depression; chills; sleep disturbances; taste alterations; loss of consciousness; reduced tactile sensitivity; tingling; worsening of near vision; ringing in the ears (tinnitus); angina (chest pain or discomfort, known as angina pectoris); irregular heartbeat; rash; hair loss; allergic skin inflammation; skin redness; red spots or dots on the skin due to small hemorrhages (purpura); skin discoloration; itchy red welts (urticaria); excessive sweating; itching; skin rash; photosensitivity reactions such as sunburn or rash; muscle pain; difficulty urinating; nocturnal urgency to urinate; breast enlargement in men; reduced sexual desire; facial swelling; feeling of malaise; weight gain or loss; exhaustion.

Rare
(may affect up to 1 in 1,000 people)
Enlargement and pain of the salivary glands; reduced number of white blood cells in the blood, which may increase the risk of infections; low number of red blood cells (anemia); bone marrow damage; restlessness; lack of interest (apathy); seizures; seeing yellow objects; dry eyes; blood clots (thrombosis or embolism); fluid accumulation in the lungs; pneumonia; inflammation of blood vessels and small skin blood vessels; inflammation of the pancreas; yellowing of the skin and eyes; acute inflammation of the gallbladder; symptoms of lupus erythematosus such as rash, joint pain, and cold fingers and hands; severe skin reactions including intense rash, urticaria, skin redness over the entire body surface, severe itching, blisters, peeling and swelling of the skin, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis), sometimes life-threatening; impaired movement; acute kidney failure; non-infectious inflammation of the kidney; reduced kidney function; fever.

Very rare
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(may affect up to 1 in 10,000 people)
Muscle stiffness; numbness of hands or feet; heart attack; stomach inflammation; gum thickening; intestinal obstruction; liver inflammation.

Not known
(frequency cannot be estimated from the available data)
Decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma).

Tremor, rigid posture, mask-like facial expression, slow movements, and unbalanced, shuffling gait.

Skin and lip cancer (non-melanoma skin cancer).

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gaduar

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

6. Package contents and other information

What Gaduar contains
The active substances are olmesartan medoxomil, amlodipine (as amlodipine besilate) and hydrochlorothiazide.
­ Gaduar 20 mg/5 mg/12.5 mg: Each film-coated tablet contains 20 mg olmesartan medoxomil, 5 mg amlodipine (as amlodipine besilate) and 12.5 mg hydrochlorothiazide.
­ Gaduar 40 mg/5 mg/12.5 mg: Each film-coated tablet contains 40 mg olmesartan medoxomil, 5 mg amlodipine (as amlodipine besilate) and 12.5 mg hydrochlorothiazide.
­ Gaduar 40 mg/5 mg/25 mg: Each film-coated tablet contains 40 mg olmesartan medoxomil, 5 mg amlodipine (as amlodipine besilate) and 25 mg hydrochlorothiazide.
­ Gaduar 40 mg/10 mg/12.5 mg: Each film-coated tablet contains 40 mg olmesartan medoxomil, 10 mg amlodipine (as amlodipine besilate) and 12.5 mg hydrochlorothiazide.
­ Gaduar 40 mg/10 mg/25 mg: Each film-coated tablet contains 40 mg olmesartan medoxomil, 10 mg amlodipine (as amlodipine besilate) and 25 mg hydrochlorothiazide.

The other components of the tablets are:
­ Tablet core: povidone; pregelatinized starch (maize); microcrystalline cellulose; anhydrous colloidal silica; lactose monohydrate; magnesium stearate.
­ Coating: polyvinyl alcohol (E1203); titanium dioxide (E171); macrogol (E1521); talc (E553b); yellow iron oxide (E172); black iron oxide (E172) (only in 20 mg/5 mg/12.5 mg film-coated tablets); red iron oxide (E172) (only in 20 mg/5 mg/12.5 mg, 40 mg/10 mg/12.5 mg, and 40 mg/10 mg/25 mg film-coated tablets).

Description of the appearance of Gaduar and contents of the pack
Gaduar 20 mg/5 mg/12.5 mg film-coated tablets are whitish-peach coloured, approximately 8.00 mm in diameter, round-shaped, with bevelled edges, film-coated tablets marked on one side with "OC1" and smooth on the other side.
Gaduar 40 mg/5 mg/12.5 mg film-coated tablets are light yellow, approximately 9.50 mm in diameter, round-shaped, with bevelled edges, film-coated tablets marked on one side with "OC2" and smooth on the other side.
Gaduar 40 mg/5 mg/25 mg film-coated tablets are light yellow, approximately 15.00 mm long, 7.00 mm wide, oval-shaped, with bevelled edges, film-coated tablets marked on one side with "OC3" and smooth on the other side.
Gaduar 40 mg/10 mg/12.5 mg film-coated tablets are brick red, approximately 9.50 mm in diameter, round-shaped, with bevelled edges, film-coated tablets marked on one side with "OC4" and smooth on the other side.
Gaduar 40 mg/10 mg/25 mg film-coated tablets are brick red, approximately 15.00 mm long, 7.00 mm wide, oval-shaped, with bevelled edges, film-coated tablets marked on one side with "OC5" and smooth on the other side.

Gaduar film-coated tablets are available in packs of 28, 56 and 98 film-coated tablets in aluminium-aluminium blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva Italia S.r.l.
Viale L. Bodio n. 37/B
20158 Milano
Italy

Manufacturers
Accord Healthcare Polska Sp. z o.o.
Ul. Lutomierska 50,
95-200, Pabianice, Poland
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park, Paola PLA
3000, Malta
LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca
08040 Barcelona, Spain
Synoptis Industrial Sp. z o.o.
ul. Rabowicka 15, 62-020
Swarzędz, Poland

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Spain, Latvia, Lithuania, Estonia, Italy: Gaduar
Germany: Olmesartan Amlodipin HCT Zentiva
Bulgaria: Xaep **
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