Sarex

Patient Information Leaflet: Information for the User

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

olmesartan medoxomil/amlodipine/hydrochlorothiazide
Equivalent medicinal product
Please read all of this leaflet carefully before you start 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, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What SAREX is and what it is used for

SAREX contains three active 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 known as “calcium antagonists”. Amlodipine also lowers blood pressure by relaxing blood vessels.
• Hydrochlorothiazide belongs to a group of medicines known as “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.
SAREX is used to treat high blood pressure:

• in adult patients whose blood pressure is not adequately controlled by the fixed-dose combination of olmesartan medoxomil and amlodipine, or
• in patients who are 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 should know before taking SAREX

Do not take SAREX:

• if you are allergic to olmesartan medoxomil, amlodipine, or to a specific group of calcium antagonists (the dihydropyridines), to hydrochlorothiazide or to 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 SAREX.

• if you have severe kidney problems.

• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

• if 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.

• if you are more than three months pregnant (it is better to avoid taking SAREX even in the early stages of pregnancy – see section “Pregnancy and breastfeeding”).

• if you have severe liver problems, if bile secretion is impaired or bile flow from the gallbladder is blocked (for example, by gallstones), or if you have jaundice (yellowing of the skin and eyes).

• if you have poor blood supply 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).

• if you have very low blood pressure.

• if blood flow from your heart is slow or obstructed. This occurs when blood vessels or valves carrying blood out of the heart are narrowed (aortic stenosis).

• if you have reduced cardiac output due to a heart attack (acute myocardial infarction). Reduced cardiac output may manifest as shortness of breath or swelling of the feet and ankles.

If you think you are in any of the conditions described above, do not take SAREX.
Warnings and precautions
Talk to your doctor or pharmacist before using SAREX.
Consult your doctor if you are taking any of the following medicines used to treat high blood pressure:

• an ACE inhibitor (for example, 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 SAREX”.
Consult your doctor if you also have any of the following health problems:

• 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 (skin eruption) 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 at high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun and UV exposure while taking SAREX.
• If you have previously experienced breathing or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulties after taking SAREX, consult a doctor immediately.

Contact your doctor if you experience any of the following symptoms:

• severe and prolonged diarrhea with significant weight loss. Your doctor will assess your symptoms and decide whether to continue this antihypertensive treatment.
• decreased vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in your eye, which may occur within hours or weeks of taking SAREX. If untreated, this increase may lead to permanent vision impairment.

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 heart attack or stroke. Your doctor will therefore carefully monitor your blood pressure.
SAREX may increase blood levels of fats and uric acid (a cause of gout – painful joint swelling). 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 imbalances include: thirst, dry mouth, muscle pain or cramps, muscle fatigue, low blood pressure (hypotension), feeling weak, lethargic, tired, drowsy or restless, nausea, vomiting, reduced need to urinate, rapid heartbeat.
Inform your doctor if these symptoms occur.
If you are scheduled for parathyroid function testing, stop taking SAREX before the test is performed.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). SAREX 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
SAREX is not recommended for children and adolescents under 18 years of age.
Other medicines and SAREX
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 SAREX. Your doctor may need to adjust the dose and/or take additional precautions:
• if you are taking an ACE inhibitor or aliskiren (see also sections “Do not take SAREX” and “Warnings and precautions”).
• Lithium (a medicine used to treat mood swings and certain types of depression) used together with SAREX may increase lithium toxicity. If you must take lithium, your doctor will monitor lithium levels in your blood.
• Diltiazem, verapamil, medicines used for heart rhythm problems and high blood pressure.
• 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.
• Intravenous vincamine, used to improve circulation in the nervous system.
• Amantadine, used for Parkinson’s disease.
• Potassium supplements, potassium-containing salt substitutes, diuretics, heparin (to thin the blood and prevent blood clots [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 sodium benzylpenicillin, an antibiotic), certain painkillers such as acetylsalicylic acid (aspirin) or salicylates. Taking these medicines together with SAREX 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), used together with SAREX may increase the risk of kidney failure. The effect of SAREX 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, used together with SAREX 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 SAREX. Your doctor may advise you to take SAREX at least 4 hours before colesevelam hydrochloride.
• Some antacids (used for indigestion or heartburn) may slightly reduce the effect of SAREX.
• Some muscle relaxants, such as baclofen and tubocurarine.
• Anticholinergic drugs, such as atropine and biperiden.
• Calcium supplements.
• Dantrolene (infusion for severe body temperature disturbances).
• 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, sirolimus, temsirolimus, everolimus, and cyclosporine) that help your body 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 health conditions such as thioridazine, chlorpromazine, levomepromazine, trifluoperazine, ciamemazine, sulpiride, amisulpride, pimozide, sultopride, tiapride, droperidol, or haloperidol.
• Treating hypoglycemia (such as diazoxide) or hypertension (beta-blockers, methyldopa), as SAREX may affect the action of these drugs.
• Treating heart rhythm problems 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 problems such as quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, bepridil, or digitalis.
• Treating cancers 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.
• Lowering blood sugar such as metformin or insulin.

Inform your doctor or pharmacist if you are taking, have recently taken, or will take any other medicine.
SAREX with food and drinks
SAREX can be taken with or without food.
People taking SAREX must not consume grapefruit or grapefruit juice. Grapefruit and its juice may increase blood levels of the active substance amlodipine, which could lead to an unpredictable increase in the blood pressure-lowering effect of SAREX.
Be cautious when drinking alcohol while taking SAREX, as some individuals may experience faintness or dizziness. If this happens, do not drink alcohol.
Elderly
If you are over 65 years of age, your doctor will regularly monitor your blood pressure with each dose increase to prevent it from dropping too low.
Pregnancy and breastfeeding
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Usually, your doctor will advise you to stop taking SAREX before becoming pregnant or as soon as you learn you are pregnant, and will recommend an alternative medicine instead of SAREX.
SAREX 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 SAREX, inform and see your doctor immediately.
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. SAREX 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 using 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.
SAREX contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.
SAREX contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take SAREX

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
The recommended dose of SAREX is one tablet per day.
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 SAREX than you should
If you take more tablets than you should, you may experience a drop in blood pressure with symptoms
such as dizziness, increased or slowed heartbeat.
If you take more tablets than prescribed or if a child accidentally ingests any, contact your doctor or the nearest emergency department immediately, taking the medicine pack or this leaflet with you.
Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may develop within 24–48 hours after ingestion.
If you forget to take SAREX
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 SAREX
It is important to continue taking SAREX unless your doctor tells you to stop.
If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse 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 many people, the following adverse effects can be serious:

• During treatment with SAREX, allergic reactions may occur, with swelling of the face, mouth and/or larynx (site of the vocal cords), associated with itching and rash (skin eruption). If this happens, stop taking SAREX and contact your doctor immediately.
• SAREX may cause excessive lowering of blood pressure in sensitive individuals. This could lead to severe dizziness or fainting. If this happens, stop taking SAREX, contact your doctor immediately and remain lying down.
• Very rarely, acute breathing difficulty may occur (signs include severe shortness of breath, fever, weakness and confusion). If this happens, stop taking SAREX and contact your doctor immediately.
• Frequency not known: if you experience yellowing of the whites of the eyes, dark urine, or skin itching, even if you have been taking SAREX for a long time, contact your doctor immediately. Your doctor will assess your symptoms and decide how to proceed with treatment for high blood pressure.

SAREX is a combination of three active substances. The following information first lists other adverse effects reported so far with the combination SAREX (in addition to those already mentioned above), followed by adverse effects known for each of the three individual substances or when two substances are administered together.

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

These are the other adverse effects with SAREX known so far:
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 throat and nose
• urinary tract infection
• dizziness; headache
• awareness of heartbeat (palpitations)
• low blood pressure
• nausea
• diarrhoea
• constipation
• cramps
• joint swelling
• feeling of urgency to urinate
• weakness
• ankle swelling
• fatigue
• laboratory test abnormalities.

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

• dizziness upon standing
• vertigo
• rapid heartbeat
• feeling of fainting
• flushing and sensation of warmth in the face
• cough
• dry mouth
• muscle weakness
• inability to achieve or maintain erection.

These are the adverse effects known for each of the components when taken alone or for two
components taken together:
These may also be adverse effects of SAREX, even though they have not been observed so far with the fixed-dose combination of olmesartan medoxomil/amlodipine/hydrochlorothiazide.

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 blocked nose
• sore throat
• difficulty breathing
• cough
• abdominal pain
• heartburn
• stomach discomfort
• flatulence
• joint or bone pain
• back pain
• skeletal pain
• blood in urine
• flu-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
• abnormally reduced appetite (anorexia)
• sleep problems; irritability
• mood changes including anxiety
• feeling low or depressed
• chills; sleep disturbances
• taste disturbances
• loss of consciousness
• reduced tactile sensitivity
• tingling sensations
• worsening of myopathy
• ringing in the ears (tinnitus)
• angina (pain or discomfort in the chest, known as angina pectoris)
• irregular heartbeat; rash (skin eruption)
• hair loss; allergic skin inflammation
• skin redness
• purple spots or dots on the skin due to small hemorrhages (purpura)
• skin color changes
• itchy red welts (urticaria)
• excessive sweating
• itching
• skin rash
• skin reactions to light such as sunburn or rash (skin eruption)
• muscle pain
• difficulty urinating
• nocturnal urge to urinate
• breast enlargement in men
• reduced sexual desire
• facial swelling
• feeling unwell
• weight gain or loss
• malaise.

Rare (may affect up to 1 in 1,000 people):

• enlargement and pain of the salivary glands
• reduction in the number of white blood cells in the blood, which may increase the risk of infections
• low red blood cell count (anaemia)
• 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 (skin eruption), joint pain and cold fingers and hands
• severe skin reactions including intense skin rash (skin eruption), urticaria, redness of the skin 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 (may affect up to 10 in 10,000 people):

• increased muscle tone
• numbness of hands or feet
• acute respiratory distress (signs include severe labored breathing, fever, weakness and confusion)
• heart attack
• inflammation of the stomach
• gum thickening
• intestinal obstruction
• inflammation of the liver.

Not known (frequency cannot be estimated from available data):

• decreased vision or eye pain (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma)
• tremor, rigid posture, mask-like face, slow movements and unbalanced, shuffling gait
• skin and lip cancer (non-melanoma skin cancer).

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

5. How to store SAREX

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.
Store in the original packaging to protect the medicine from light. This medicine does not require any special storage temperature conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

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

The other components are:
Tablet core: Microcrystalline cellulose, monohydrate lactose, povidone, crospovidone, sodium starch glycolate, hydrated colloidal silica, magnesium stearate
Coating:
SAREX 20 mg/5 mg/12.5 mg:
Opadry II 85F18378 White coating: Partially hydrolysed polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol (E1521), talc (E553b)
SAREX 40 mg/5 mg/12.5 mg and 40 mg/5 mg/25 mg: Opadry II 85F22055 Yellow coating:
Partially hydrolysed polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol (E1521), talc (E553b), yellow iron oxide (E172)
SAREX 40 mg/10 mg/12.5 mg and 40 mg/10 mg/25 mg: Opadry II 85F94526 Pink coating:
Partially hydrolysed polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol (E1521), talc (E553b), red iron oxide (E172).

Description of the appearance of SAREX and pack contents
SAREX 20 mg/5 mg/12.5 mg: White, round tablet with bevelled edges, marked “OA” on one side and “05” on the other side.
SAREX 40 mg/5 mg/12.5 mg: Yellow, round tablet with bevelled edges, marked “OA” on one side and “06” on the other side.
SAREX 40 mg/10 mg/12.5 mg: Pink, round tablet with bevelled edges, marked “OA” on one side and “03” on the other side.
SAREX 40 mg/5 mg/25 mg: Yellow, capsule-shaped tablet with bevelled edges, marked “OA” on one side and “04” on the other side.
SAREX 40 mg/10 mg/25 mg: Pink, capsule-shaped tablet with bevelled edges, marked “OA” on one side and “02” on the other side.

SAREX 20 mg/5 mg/12.5 mg film-coated tablets
SAREX 40 mg/5 mg/12.5 mg film-coated tablets
SAREX 40 mg/10 mg/12.5 mg film-coated tablets
SAREX 40 mg/5 mg/25 mg film-coated tablets
SAREX 40 mg/10 mg/25 mg film-coated tablets
Blister packs of 28 tablets
Not all pack sizes may be marketed.

Marketing Authorization Holder
Day Zero ehf.
Reykjavikurvegi, 62
Hafnarfjördur 220
Iceland

Manufacturer
Teva Operations Poland Sp. z.o.o,
Ul. Mogilska 80, Kraków, 31-546
Poland
or
Balkanpharma-Dupnitsa AD
3 Samokovsko Shosse Str., Dupnitsa, 2600
Bulgaria

This medicinal product has been authorised in the European Economic Area Member States under the following names:
Netherlands: Olsartide