Olmetrivart

Package leaflet: Information for the user

Olmetrivart 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
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 further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their signs and
symptoms are similar to yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.
Contents of this leaflet

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

1. What Olmetrivart is and what it is used for

Olmetrivart contains three substances called olmesartan medoxomil, amlodipine (as amlodipine
besylate) and hydrochlorothiazide. All of these 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 substances known as “thiazide diuretics” (medicines that stimulate diuresis). It lowers blood pressure by helping the body eliminate excess water, by increasing urine production through the kidneys.
The combined action of these substances contributes to lowering blood pressure.
Olmetrivart is used to treat high blood pressure:
in adult patients whose blood pressure is not adequately controlled by the fixed combination of olmesartan medoxomil and amlodipine, or
in patients who are already taking a fixed combination of olmesartan medoxomil and hydrochlorothiazide plus amlodipine as a single tablet, or a fixed combination of olmesartan medoxomil and amlodipine plus hydrochlorothiazide as a single tablet.

2. What you should know before taking Olmetrivart

Do not take Olmetrivart 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 Olmetrivart.
you have severe kidney problems.
you have 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 Olmetrivart even in the early stages of pregnancy – see section “Pregnancy and breastfeeding”).
you suffer from severe liver problems, if bile secretion is impaired or bile flow is obstructed (for example, by 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 blocked. This occurs when blood vessels or valves carrying blood away from the heart narrow (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 conditions described above, do not take Olmetrivart.
For athletes: using this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.

Warnings and precautions
Talk to your doctor or pharmacist before taking Olmetrivart if:
you have previously experienced respiratory or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulty after taking Olmetrivart, consult a doctor immediately.
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.
Contact your doctor if, after taking Olmetrivart, you experience abdominal pain, nausea, vomiting, or diarrhea. Your doctor will decide whether treatment should continue. Do not stop taking Olmetrivart on your own.
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 Olmetrivart if”:
Inform your doctor if you have any of the following health conditions:

• Kidney problems or kidney transplant. Liver disease. Heart failure or heart valve or heart muscle problems. Severe vomiting, diarrhea, treatment with high doses of diuretics, or if you are on a low-salt diet. Elevated potassium levels in the blood. Adrenal gland disorders (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 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 skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun and UV exposure while taking Olmetrivart.
  Inform your doctor if any of the following symptoms occur:
  severe and prolonged diarrhea with significant weight loss. Your doctor will assess your symptoms and decide whether to continue this antihypertensive treatment;
  vision changes 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, which may occur within hours or weeks of taking Olmetrivart. If untreated, this increase in pressure 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.
  Olmetrivart may increase blood lipid and uric acid levels (causing gout – painful joint swelling). Your doctor may wish to perform periodic blood tests to monitor these conditions.
  Blood levels of certain substances called electrolytes may change. Your doctor may wish 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 Olmetrivart 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). Olmetrivart 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)
Olmetrivart is not recommended for children and adolescents under 18 years of age.

Other medicines and Olmetrivart
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 Olmetrivart. Your doctor may need to adjust the dose and/or take other precautions:
if you are taking an ACE inhibitor or aliskiren (see also sections “Do not take Olmetrivart if” and “Warnings and precautions”).
Lithium (a medicine used to treat mood swings and certain types of depression) taken together with Olmetrivart may increase lithium toxicity. If you are to take lithium, your doctor will monitor your blood lithium levels.
Diltiazem, verapamil, medicines used for heart rhythm disorders 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 in 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 Olmetrivart 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 Olmetrivart may increase the risk of kidney failure. The effectiveness of Olmetrivart may be reduced by NSAIDs. When high doses of salicylates are taken, central nervous system toxic effects may be increased.
Sedatives, hypnotics, and antidepressants, taken together with Olmetrivart, may cause a sudden drop in blood pressure upon standing.
Colesevelam hydrochloride, a medicine that lowers cholesterol levels in the blood, which may reduce the effect of Olmetrivart. Your doctor may advise you to take Olmetrivart at least 4 hours before colesevelam hydrochloride.
Some antacids (used for indigestion or stomach acidity) may slightly reduce the effectiveness of Olmetrivart.
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, cyclosporine) that help your body accept transplanted organs.
Additionally, 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, levomepromazine, trifluoperazine, cyamemazine, sulpiride, amisulpride, pimozide, sultopride, tiapride, droperidol, or haloperidol.
Treating hypoglycemia (e.g., diazoxide) or hypertension (beta-blockers, methyldopa), as Olmetrivart 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 disorders 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.
Reducing blood sugar levels such as metformin or insulin.
Inform your doctor or pharmacist if you are taking, have recently taken, or will take any other medicines.

Olmetrivart with food and drinks
Olmetrivart can be taken with or without food.
People taking Olmetrivart must not consume grapefruit or grapefruit juice, as grapefruit and its juice may increase blood levels of the active ingredient amlodipine, potentially causing an unpredictable increase in the hypotensive effect of Olmetrivart.
Be cautious when drinking alcohol while taking Olmetrivart, as some individuals may feel weak or confused. 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 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 Olmetrivart before becoming pregnant or as soon as you learn you are pregnant, and will recommend an alternative medicine. Olmetrivart 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 Olmetrivart, inform and see your doctor immediately.

Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. It has been shown that amlodipine passes into breast milk in small amounts. Olmetrivart is not recommended for breastfeeding women, and your doctor may choose an alternative treatment if you wish to breastfeed.
If you are pregnant, think you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking any medicine.

Driving and using machines
You may experience drowsiness, confusion, 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.

Olmetrivart contains lactose
If your doctor has informed you that you have an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Olmetrivart

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 Olmetrivart is one tablet daily.
• 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 with grapefruit juice.
• If possible, take your daily dose at the same time each day, for example with breakfast.

If you take more Olmetrivart 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 a faster or slower heartbeat.
Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may develop within 24–48 hours after ingestion.
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 Olmetrivart
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 Olmetrivart
It is important to continue taking Olmetrivart 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 side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. If they do occur, they are mostly mild and do not require discontinuation of treatment.
Although they do not occur in all people, the following side effects can be serious:
During treatment with this medicine, allergic reactions may occur, with swelling of the face, mouth and/or larynx (the site of the vocal cords), associated with itching and skin rash. If this happens, stop taking Olmetrivart and contact your doctor immediately.
Olmetrivart may cause excessive lowering of blood pressure in sensitive individuals. This could lead to severe dizziness or fainting. If this happens, stop taking Olmetrivart, contact your doctor immediately and remain lying down.
Frequency not known: if you experience yellowing of the whites of the eyes, dark urine, or skin itching, even if you have been on Olmetrivart therapy for a long time, contact your doctor immediately. The doctor will evaluate your symptoms and decide how to proceed with treatment for high blood pressure.
Olmetrivart is a combination of three active substances. The information below first lists other side effects reported so far with the combination Olmetrivart (in addition to those already mentioned above), and secondly, those side effects known for each of the three substances when taken separately or when two substances are administered together.
To give you an idea of how many patients have experienced these side effects, they have been categorized as common, uncommon, rare, and very rare.
These are the other side effects with Olmetrivart 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 the throat and nose; urinary tract infection; dizziness; headache; awareness of heartbeat; low blood pressure; nausea; diarrhea; constipation; cramps; joint swelling; 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 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 when taken alone or for two components taken together:
These may also be side effects of Olmetrivart, even if they have not yet been observed 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; vision disturbances (including double and blurred vision); runny or stuffy nose; sore throat; breathing difficulty; cough; abdominal pain; heartburn; gastric 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; abnormal reduction 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; small red spots or patches on the skin due to minor bleeding (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)
Swelling 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; yellow vision; dry eyes; blood clots (thrombosis, embolism); fluid accumulation in the lungs; pneumonia; inflammation of blood vessels and small skin blood vessels; pancreatitis; 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, 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); impaired movement; acute kidney failure; non-infectious kidney inflammation; reduced kidney function; fever, intestinal angioedema: swelling in the intestine presenting with symptoms such as abdominal pain, nausea, vomiting and diarrhea.
Very rare
(may affect up to 1 in 10,000 people)
Acute respiratory distress (signs include severe shortness of breath, fever, weakness and confusion); muscle rigidity; numbness of hands or feet; heart attack; stomach inflammation; gum thickening; intestinal obstruction; liver inflammation.
Not known
(frequency cannot be determined from available data)
Vision loss 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 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 can 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 Olmetrivart

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 carton and on the blister after
"EXP". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine 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 Olmetrivart contains
The active substances are olmesartan medoxomil, amlodipine (as amlodipine besilate) and
hydrochlorothiazide.
Olmetrivart 20 mg/5 mg/12.5 mg: Each film-coated tablet contains 20 mg of olmesartan medoxomil, 5 mg of amlodipine (as besilate) and 12.5 mg of hydrochlorothiazide.
Olmetrivart 40 mg/5 mg/12.5 mg: Each film-coated tablet contains 40 mg of olmesartan medoxomil, 5 mg of amlodipine (as besilate) and 12.5 mg of hydrochlorothiazide.
Olmetrivart 40 mg/5 mg/25 mg: Each film-coated tablet contains 40 mg of olmesartan medoxomil, 5 mg of amlodipine (as besilate) and 25 mg of hydrochlorothiazide.
Olmetrivart 40 mg/10 mg/12.5 mg: Each film-coated tablet contains 40 mg of olmesartan medoxomil, 10 mg of amlodipine (as besilate) and 12.5 mg of hydrochlorothiazide.
Olmetrivart 40 mg/10 mg/25 mg: Each film-coated tablet contains 40 mg of olmesartan medoxomil, 10 mg of amlodipine (as besilate) and 25 mg of hydrochlorothiazide.

The other components are:
Tablet core: povidone; pregelatinized maize starch; 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 film-coated tablets of 20 mg/5 mg/12.5 mg); red iron oxide (E172) (only in film-coated tablets of 20 mg/5 mg/12.5 mg, 40 mg/10 mg/12.5 mg, 40 mg/10 mg/25 mg).

Description of the appearance of Olmetrivart and the contents of the pack
Olmetrivart 20 mg/5 mg/12.5 mg film-coated tablets are approximately 8 mm in diameter, film-coated, peach-white in colour, round-shaped with bevelled edges, marked with the code “OC1” on one side and smooth on the other.
Olmetrivart 40 mg/5 mg/12.5 mg film-coated tablets are light yellow, film-coated tablets, approximately 9.5 mm in diameter, round-shaped with bevelled edges, marked with the code “OC2” on one side and smooth on the other.
Olmetrivart 40 mg/5 mg/25 mg film-coated tablets are light yellow, film-coated, oval-shaped with bevelled edges, approximately 15.00 mm long and 7.00 mm wide, marked with the code “OC3” on one side and smooth on the other.
Olmetrivart 40 mg/10 mg/12.5 mg film-coated tablets are brick-red, film-coated, approximately 9.50 mm in diameter, round-shaped with bevelled edges, marked with the code “OC4” on one side and smooth on the other.
Olmetrivart 40 mg/10 mg/25 mg film-coated tablets are brick-red, film-coated, oval-shaped with bevelled edges, approximately 15.00 mm long and 7.00 mm wide, marked with the code “OC5” on one side and smooth on the other.

Carton pack containing aluminium-aluminium blisters in pack sizes of:
28 film-coated tablets
28 x 1 film-coated tablet
98 film-coated tablets
98 x 1 film-coated tablet

Not all pack sizes may be marketed.

Marketing Authorization Holder
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milan, Italy

Manufacturers
LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca, Barcelona,
08040 Barcelona, Spain
Synoptis Industrial Sp. z o.o.
ul. Rabowicka 15, 62-020
Swarzędz, Poland
Mylan Germany GmbH
Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1
Bad Homburg v. d. Hoehe
Hesse, 61352,
Germany