Trilond

Patient Information Leaflet: Information for the Patient

Trilond 16 mg/5 mg/20 mg tablets, 16 mg/10 mg/20 mg tablets, 16 mg/5 mg/40 mg tablets, 16 mg/10 mg/40 mg tablets

candesartan cilexetil/amlodipine/atorvastatin
Please read this leaflet carefully before taking this medicine, as 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 other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Trilond is and what it is used for

Trilond tablets contain three active substances called candesartan cilexetil, amlodipine, and atorvastatin.
Candesartan cilexetil belongs to a group of medicines called angiotensin II receptor antagonists. It works by relaxing and widening blood vessels. This helps lower blood pressure. It also allows the heart to pump blood more easily throughout the body.
Amlodipine belongs to a group of medicines called calcium channel blockers. In patients with high blood pressure, it works by relaxing blood vessels, thereby allowing blood to flow through them more easily.
Atorvastatin belongs to a group of medicines known as statins, which regulate lipid (fat) levels. It works by reducing blood levels of lipids known as cholesterol and triglycerides.
This medicine is used in adult patients to treat high blood pressure (essential hypertension) associated with high cholesterol levels (primary hypercholesterolaemia) or with high cholesterol and fat (triglyceride) levels simultaneously (combined or mixed hyperlipidaemia).
Instead of taking candesartan, amlodipine, and atorvastatin as separate tablets, you will receive one Trilond tablet containing the three active substances at the same dosage.

2. What you need to know before taking Trilond

Do not take Trilond

• if you are allergic to candesartan cilexetil, amlodipine, or any other calcium channel blocker, atorvastatin, or any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant or planning to become pregnant;
• if you are breastfeeding;
• if you are a woman of childbearing age and are not using a reliable method of contraception;
• if you have severe low blood pressure (hypotension);
• if you suffer from narrowing of the aortic valve of the heart (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body);
• if you suffer from heart failure following a heart attack;
• if you have any liver disease or if your liver function test results are unexplainedly abnormal;
• if you have severe liver disease or biliary obstruction (a problem with bile drainage from the gallbladder);
• if you are taking glecaprevir/pibrentasvir in combination for the treatment of hepatitis C;
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

If you have any doubts whether any of the above points apply to you, consult your doctor or pharmacist before taking Trilond.

Warnings and precautions

Talk to your doctor or pharmacist before taking Trilond.

You must inform your doctor if you have or have had any of the following medical conditions:

• heart problems, recent heart attack, or heart failure;
• liver problems or a history of liver disease;
• kidney problems, are on dialysis, or have recently undergone a kidney transplant;
• vomiting, recent severe vomiting, or diarrhea;
• a disease of the adrenal gland known as Conn’s syndrome (also called primary hyperaldosteronism);
• stroke or previous stroke with brain bleeding, or small fluid-filled pockets in the brain following prior strokes;
• 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, or aliskiren;
• if you are taking an ACE inhibitor together with a medicine belonging to a class known as mineralocorticoid receptor antagonists (MRAs). These medicines are used to treat heart failure (see section “Other medicines and Trilond”);
• if you have a severe increase in blood pressure (hypertensive crisis);
• if you suffer from severe respiratory insufficiency;
• if you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (used to treat bacterial infections). The combination of fusidic acid and atorvastatin may lead to life-threatening muscle problems (rhabdomyolysis);
• if you have reduced thyroid activity (hypothyroidism);
• if you have had recurrent or unexplained muscle pain, or if you or a family member have had muscle problems;
• if you have had previous muscle problems during treatment with other lipid-lowering medicines (e.g., other medicines known as “statins” or “fibrates”);
• if you have or have had myasthenia (a disease characterized by generalized muscle weakness, including in some cases the muscles used for breathing) or ocular myasthenia (a disease causing weakness of the eye muscles), as statins may sometimes worsen myasthenia or trigger its onset (see section 4);
• if you regularly consume large amounts of alcohol.

Contact your doctor if, after taking Trilond, you experience abdominal pain, nausea, vomiting, or diarrhea. Your doctor will decide whether treatment should continue. Do not stop taking Trilond on your own.

Muscle-related side effects

Your doctor may want to monitor your kidney function, blood pressure, and order regular blood tests. This allows your doctor to monitor levels of electrolytes (such as potassium) in your blood and also to assess the risk of developing muscle-related side effects. It is known that the risk of muscle-related side effects, such as rhabdomyolysis, increases when certain medicines are taken concurrently (see section 2 “Other medicines and Trilond”).

Additionally, inform your doctor or pharmacist if you experience persistent muscle weakness.

Further tests and medicines may be needed to diagnose and treat this condition.

Diabetes

During treatment with this medicine, your doctor will closely monitor you if you have diabetes or are at risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and fats in your blood, are overweight, and have high blood pressure.

Surgery

If you are scheduled for surgery, inform your doctor or dentist that you are taking Trilond. This is because this medicine, when combined with certain anesthetics, may cause an excessive drop in blood pressure.

See also the information provided in the section “Do not take Trilond”.

Children and adolescents

The use of this medicine is not recommended in children and adolescents under 18 years of age.

Other medicines and Trilond

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Trilond may alter the effect of other medicines, and some medicines may affect Trilond. This type of interaction may make one or both medicines less effective.

Conversely, it may also increase the risk or severity of side effects, including a serious but rare condition of muscle breakdown known as rhabdomyolysis, described in section 4. If you are taking certain medicines, your doctor may need to perform blood tests from time to time.

In particular, inform your doctor if you are taking any of the following medicines, as your doctor may need to adjust the dose and/or take other precautions:

• other medicines that help lower blood pressure, including beta-blockers such as bisoprolol or nebivolol, diazoxide, ACE inhibitors such as enalapril, captopril, lisinopril, or ramipril, and aliskiren (see “Do not take Trilond” and “Warnings and precautions”);
• if you are being treated with an ACE inhibitor together with certain other medicines for heart failure, known as mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone;
• medicines to relieve pain and inflammation, including non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, diclofenac, celecoxib, etoricoxib, or phenazone, and acetylsalicylic acid (if you are taking more than 3 g per day);
• medicines that increase potassium levels in the blood, such as potassium supplements or potassium-containing salt substitutes;
• medicines to thin the blood, such as heparin or warfarin;
• the antibiotic cotrimoxazole, also known as trimethoprim/sulfamethoxazole;
• tablets that promote diuresis or diuretics;
• lithium, a medicine used to treat mental health disorders;
• protease inhibitors used to treat HIV, e.g., ritonavir, lopinavir, atazanavir, indinavir, nelfinavir, darunavir, or the combination tipranavir/ritonavir;
• antibiotics or antifungal medicines, such as erythromycin, clarithromycin, telithromycin, ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole, rifampicin, or fusidic acid*;
• over-the-counter medicines: St. John’s wort (Hypericum perforatum);
• heart medicines, such as verapamil, diltiazem, digoxin, or amiodarone;
• dantrolene, an infusion used for severe disturbances in body temperature;
• medicines used to alter the function of the immune system, such as tacrolimus, sirolimus, temsirolimus, cyclosporine, or everolimus;
• medicines used to regulate lipid levels, such as gemfibrozil, other fibrates, colestipol, or ezetimibe;
• letermovir, a medicine that helps prevent cytomegalovirus infection;
• medicines used to treat hepatitis C, e.g., telaprevir, boceprevir, or the combination of elbasvir/grazoprevir, or ledipasvir/sofosbuvir;
• oral contraceptives;
• stiripentol, an anticonvulsant for epilepsy;
• cimetidine, a medicine used to treat heartburn and peptic ulcers;
• colchicine, for the treatment of gout;
• medicines for digestive problems containing aluminium or magnesium, such as antacids;
• daptomycin (a medicine used to treat complicated skin and soft tissue infections and bloodstream infections).

*If you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will tell you when it is safe to restart treatment with Trilond. Taking atorvastatin with fusidic acid may rarely cause weakness, tenderness, or muscle pain (rhabdomyolysis). For more information on rhabdomyolysis, see section 4.

Trilond with food, drinks, and alcohol

Alcohol

When Trilond is prescribed for you, consult your doctor before drinking alcohol. Alcohol may make you feel weak or cause dizziness. For more information, see section 2 “Warnings and precautions”.

Grapefruit juice

Patients taking Trilond must not consume grapefruit or grapefruit juice, as these may increase blood levels of the active ingredient amlodipine, which could lead to an unpredictable increase in the blood pressure-lowering effect of this medicine. Large amounts of grapefruit juice may also increase the effect of the active ingredient atorvastatin.

Pregnancy and breastfeeding

Pregnancy

You must inform your doctor if you suspect (or are planning) pregnancy. Your doctor will normally advise you to stop taking Trilond before becoming pregnant or as soon as pregnancy is confirmed, and will prescribe another medicine instead.

Trilond must not be taken during pregnancy as it may cause serious harm to the unborn child.

Breastfeeding

You must inform your doctor if you are breastfeeding or intend to breastfeed. Breastfeeding women must not take this medicine. If you wish to breastfeed, your doctor may choose another treatment for you, especially if your baby is a newborn or premature.

It has been shown that amlodipine passes into breast milk in small amounts.

Do not take this medicine if you are a woman of childbearing age unless you are using an effective method of contraception.

Driving and using machines

This medicine may impair your ability to drive or operate machinery. If the tablets cause you nausea, dizziness, fatigue, or headache, do not drive or operate machinery.

Trilond contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially ‘sodium-free’.

3. How to take Trilond

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is 1 tablet per day.
To achieve a daily dose of 8 mg of candesartan cilexetil, 5 mg of amlodipine and 20 mg of atorvastatin, the recommended daily dose is ½ tablet of Trilond 16 mg/10 mg/40 mg tablets.
While taking Trilond, you must continue to follow a cholesterol-lowering diet.
Swallow the tablet whole with a glass of water at the same time each day, with or without food.

If you take more Trilond than you should
Contact your doctor immediately if you take too many Trilond tablets.
Taking too many tablets may cause an excessive or even dangerous drop in blood pressure. You may experience dizziness, lightheadedness, fainting, or weakness. If the drop in blood pressure is severe enough, shock may occur. Your skin may become cold and clammy, and you may lose consciousness. Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may appear up to 24–48 hours after ingestion.

If you forget to take Trilond
Do not worry. If you forget to take a tablet, skip that dose completely. Take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you stop taking Trilond
Your doctor will advise you how long to take this medicine.
If you stop treatment before being told to do so, your condition may return. Therefore, do not stop treatment without first consulting your doctor.

If you have any questions 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 everybody gets them.
Stop taking Trilond and contact your doctor immediately if you experience any of the following reactions:

• Sudden wheezing, chest pain, difficulty breathing, with or without swelling of the face, eyelids, lips, tongue and/or throat, which may cause severe difficulty swallowing and breathing.

• Severe skin reactions including intense rash, hives, widespread skin redness, severe itching, severe peeling and swelling of the skin, blistering of the
  skin, mouth, eyes, genitals, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions.

• Rash with reddish spots, particularly on the palms of the hands or soles of the feet, which may develop into blisters.

• Weakness, tenderness, pain or injury to muscles or red-brown discoloration of urine; especially if you also feel unwell and have a high temperature, this may be due to abnormal muscle breakdown (rhabdomyolysis). Abnormal muscle breakdown does not always resolve even after stopping atorvastatin, and may be life-threatening and cause kidney problems.

• Heart attack, irregular heartbeat.

• Inflamed (swollen) pancreas, which may cause severe abdominal and back pain, accompanied by a general feeling of severe illness (pancreatitis).

• Unusual or unexpected bleeding or bruising, which may suggest a liver problem. You should consult your doctor as soon as possible.

• Lupus-like disease syndrome (including rash, joint disorders and effects on blood cells).

Blood-related side effects
Trilond may cause a reduction in the number of white blood cells. Your resistance to infections may decrease, and you may experience fatigue, infection or fever. If this occurs, consult your doctor. Your doctor may occasionally prescribe blood tests to check whether Trilond has had any effect on your blood (agranulocytosis).
Other possible side effects:
Very common (may affect more than 1 in 10 people)

• Edema (fluid retention).

Common (may affect up to 1 in 10 people)

• Respiratory infections.
• Nasal inflammation, sore throat, nosebleeds.
• Increased blood sugar levels (hyperglycaemia; if you have diabetes, you should continue to monitor your blood sugar levels carefully).
• Headache.
• Dizziness, drowsiness.
• Vision disorders, double vision.
• Palpitations (awareness of your heartbeat).
• Flushing.
• Shortness of breath (dyspnoea).
• Abdominal pain, altered bowel habits, nausea, diarrhoea, indigestion, constipation, flatulence.
• Swelling of ankles and joints, muscle cramps, muscle spasms, muscle pain, joint pain, limb pain, back pain.
• Fatigue, weakness.
• Abnormal liver function blood tests, increased creatine kinase in the blood.

Uncommon (may affect up to 1 in 100 people)

• Loss of appetite (anorexia), decreased blood sugar levels (if you have diabetes, you should continue to monitor your blood sugar levels carefully).
• Mood changes, anxiety, depression, insomnia, nightmares.
• Tremor, fainting, taste disturbances, memory loss.
• Numbness or tingling in limbs, reduced sensation to pain or touch.
• Blurred vision.
• Ringing in the ears and/or head (tinnitus).
• Low blood pressure.
• Cough, cold/runny nose caused by inflammation of the nasal lining (rhinitis).
• Vomiting (nausea), belching, dry mouth.
• Changes in liver function, including liver inflammation (hepatitis). You may notice fatigue, yellowing of the skin and whites of the eyes, and flu-like symptoms.
• Hair loss, increased sweating, itching, red spots on the skin, skin discoloration.
• Neck pain, muscle fatigue.
• Urinary disorders, increased need to urinate at night, frequent need to urinate.
• Inability to achieve an erection, discomfort or breast enlargement in men (gynaecomastia).
• Pain, feeling unwell, swelling, particularly in the ankles (oedema), increased body temperature.
• Weight gain or loss.
• Urine tests positive for white blood cells.

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

• Confusion.
• Cholestasis (yellowing of the skin and whites of the eyes).
• Tendon injuries.
• Skin rash which may appear on the skin or mouth ulcers (drug-induced lichenoid reaction).

Very rare (may affect up to 1 in 10,000 people)

• Reduction in red or white blood cells. You may notice fatigue, infection or fever.
• Reduction in blood platelets which may cause unexpected bleeding or bruising.
• Increased potassium levels in the blood. In severe cases, you may notice weakness, lack of energy or muscle cramps.
• Reduced sodium levels in the blood.
• Hearing loss.
• Inflammation of blood vessels.
• Swelling, bleeding of the gums.
• Abdominal swelling (gastritis).
• Intestinal angioedema: swelling in the intestine presenting with symptoms such as abdominal pain, nausea, vomiting and diarrhoea.
• Yellowing of the skin (jaundice), increased liver enzymes with possible effect on certain clinical tests, liver failure.
• Increased muscle tension.
• Light sensitivity.
• Disorders related to stiffness, tremor, muscle weakness, tingling or numbness and/or movement disorders.
• Kidney failure, particularly if you already have kidney problems or heart failure.

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

• Tremor, rigid posture, mask-like facial expression, slow movements and shuffling gait.
• Persistent muscle weakness.
• Myasthenia gravis (a disease causing generalized muscle weakness, possibly affecting in some cases the muscles used for breathing).
• Ocular myasthenia (a disease causing weakness of the eye muscles).
• Contact your doctor if you experience arm or leg weakness that worsens after periods of activity, double vision or drooping eyelids, difficulty swallowing or shortness of breath.

Possible side effects reported with some statins (medicines of the same type):

• Sexual difficulties.
• Depression.
• Breathing problems including persistent cough and/or shortness of breath or fever.
• Diabetes. This is more likely if you have high levels of sugar and fats in your blood, are overweight and have high blood pressure.
• Your doctor will monitor you during treatment with this medicine.

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 Trilond

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature. Store in the original packaging to protect the medicine from light.
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. Contents of the pack and other information

What Trilond contains
The active substances are:
Trilond 16 mg/5 mg/20 mg tablets:
The active substances in one tablet are 16 mg of candesartan cilexetil, 5 mg of amlodipine (as amlodipine
besilate) and 20 mg of atorvastatin (as atorvastatin calcium trihydrate).
Trilond 16 mg/10 mg/20 mg tablets:
The active substances in one tablet are 16 mg of candesartan cilexetil, 10 mg of amlodipine (as
amlodipine besilate) and 20 mg of atorvastatin (as atorvastatin calcium trihydrate).
Trilond 16 mg/5 mg/40 mg tablets:
The active substances in one tablet are 16 mg of candesartan cilexetil, 5 mg of amlodipine (as amlodipine
besilate) and 40 mg of atorvastatin (as atorvastatin calcium trihydrate).
Trilond 16 mg/10 mg/40 mg tablets:
The active substances in one tablet are 16 mg of candesartan cilexetil, 10 mg of amlodipine (as
amlodipine besilate) and 40 mg of atorvastatin (as atorvastatin calcium trihydrate).
The other components are: calcium carbonate (E 170), calcium carmellose (E 466), microcrystalline cellulose (E
460), sodium croscarmellose (E 468), hypromellose (E 463), magnesium stearate (E 470b), mannitol
(E 421), macrogol 8000 (E 1521), polysorbate 80 (E 433), pregelatinized starch (E 1422).

Description of the appearance of Trilond and contents of the pack
Trilond 16 mg/5 mg/20 mg tablets:
Tablets are white to off-white, round, biconvex, with "16" engraved on one side and "C H" on the other side (size: diameter approximately 9.5 mm).
Trilond 16 mg/10 mg/20 mg tablets:
Tablets are white to off-white, round, biconvex, with "C A" engraved on one side and "A" on the other side (size: diameter approximately 9.5 mm).
Trilond 16 mg/5 mg/40 mg tablets:
Tablets are white to off-white, oval, biconvex, with "16 5" engraved on one side and "40" on the other side (size: length approximately 18.2 mm).
Trilond 16 mg/10 mg/40 mg tablets:
Tablets are white to off-white, oval, biconvex, with a central groove on both sides, and "16 10" engraved on one side and "40" on the other side (size: length approximately 18.2 mm).
The tablet can be divided into equal doses.
30 tablets in OPA/aluminum/PVC blisters covered with an aluminum foil, packed in a cardboard carton.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
OP Pharma S.r.l., via Monte Rosa 61, 20149 Milano, Italy
Manufacturer
Bluepharma Industria Farmaceutica S.A., São Martinho do Bispo, 3045-016 Coimbra, Portugal