Perindopril and amlodipine HCS

Patient Information Leaflet

Perindopril and Amlodipine HCS 4 mg/5 mg tablets, 4 mg/10 mg tablets, 8 mg/5 mg tablets, 8 mg/10 mg tablets

Perindopril tert-butylamine/Amlodipine
Equivalent medicine
Please read all of 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 other people, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Perindopril and Amlodipine HCS is and what it is used for

Perindopril and Amlodipine HCS is prescribed for the treatment of high blood pressure (hypertension) and/or
for the treatment of stable coronary artery disease (a condition in which blood supply to the heart
is reduced or blocked). Patients who are already taking perindopril and amlodipine as separate tablets
may instead take a single tablet of Perindopril and Amlodipine HCS containing both active substances.
Perindopril and Amlodipine HCS is a combination of two active substances, perindopril and amlodipine.
Perindopril is an ACE inhibitor (angiotensin-converting enzyme inhibitor). Amlodipine is a calcium
antagonist (belonging to a class of medicines called dihydropyridines). Together, they act to dilate and relax blood vessels,
allowing blood to flow more easily and helping the heart maintain adequate blood flow.

2. What you should know before taking Perindopril and amlodipine HCS

Do not take Perindopril and amlodipine HCS:

• if you are allergic (hypersensitive) to perindopril or any ACE inhibitor, or to amlodipine or any other calcium antagonist, or to any of the other ingredients of Perindopril and amlodipine HCS,
• if you are more than 3 months pregnant (Perindopril and amlodipine HCS is best avoided even in early pregnancy – see the section on pregnancy),
• if you have previously experienced symptoms such as breathlessness, facial or tongue swelling, severe itching, or serious skin rashes during prior treatment with ACE inhibitors, or if you or a family member has had these symptoms in other circumstances (a condition called angioedema),
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren,
• if you have narrowing of the aortic valve (aortic stenosis) or if you are suffering from cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body),
• if you suffer from severe low blood pressure (hypotension),
• if you have heart failure following a heart attack.

Warnings and precautions
If you have any of the following conditions, consult your doctor before taking Perindopril and amlodipine HCS:

• if you suffer from hypertrophic cardiomyopathy (a heart muscle disease) or renal artery stenosis (narrowing of the artery supplying blood to the kidney),
• if you have heart failure,
• if you have a severe increase in blood pressure (hypertensive crisis),
• if you have any other heart condition,
• if you have liver problems,
• if you have kidney problems or are on dialysis,
• if you have a collagen vascular disease (connective tissue disease) such as systemic lupus erythematosus or scleroderma,
• diabetes,
• if you are on a salt-restricted diet or use salt substitutes containing potassium (a well-balanced level of potassium in the blood is essential),
• if you are elderly and your dose needs to be increased,
• if you are taking any of the following medicines used to treat high blood pressure:
  • an angiotensin receptor blocker (ARB) (also known as sartans, e.g. valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes,
  • aliskiren.
• if you are taking any of the following medicines, the risk of angioedema is increased:
  • racecadotril (used to treat diarrhoea),
  • sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of so-called mTOR inhibitors (used to prevent rejection of transplanted organs).

Your doctor may check your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals.
See also the section “Do not take Perindopril and amlodipine HCS”.
You must inform your doctor if you think you are (or may become) pregnant. Perindopril and amlodipine HCS is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn baby when used at this stage (see section on pregnancy).
When taking Perindopril and amlodipine HCS, you must inform your doctor or healthcare professional:

• if you are about to undergo general anaesthesia and/or major surgery,
• if you have recently suffered from diarrhoea or vomiting (a state of illness),
• if you are due to undergo LDL apheresis (removal of cholesterol from your blood via a machine),
• if you are about to undergo desensitisation treatment to reduce the effects of an allergy to bee or wasp stings.

Children and adolescents
Perindopril and amlodipine HCS is not recommended for use in children and adolescents.

Other medicines and Perindopril and amlodipine HCS
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
You must avoid Perindopril and amlodipine HCS with:

• lithium (used to treat mania or depression),
• estramustine (used in cancer therapy),
• potassium-sparing diuretics (spironolactone, triamterene), potassium supplements, or salt substitutes containing potassium.

Treatment with Perindopril and amlodipine HCS may be affected by other medicines. Make sure to inform your doctor if you are taking any of the following medicines, as special care may be needed:

• other medicines for high blood pressure, including angiotensin II receptor blockers (ARBs), aliskiren (see also information in the sections "Do not take Perindopril and amlodipine HCS" and "Warnings and precautions with Perindopril and amlodipine HCS"), or diuretics (medicines that increase the amount of urine produced by the kidneys),
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) for pain relief or high-dose acetylsalicylic acid,
• medicines for the treatment of diabetes (such as insulin),
• medicines for mental disorders such as depression, anxiety, schizophrenia, etc. (e.g. tricyclic antidepressants, antipsychotics, imipramine-type antidepressants, neuroleptics),
• immunosuppressants (medicines that may reduce the body's defence mechanism) used to treat autoimmune diseases or after organ transplantation (e.g. cyclosporine),
• allopurinol (for the treatment of gout),
• procainamide (for the treatment of irregular heartbeat),
• vasodilators including nitrates (substances that dilate blood vessels),
• heparin (a medicine used to make blood less thick),
• ephedrine, noradrenaline, or adrenaline (medicines used to treat low blood pressure, shock, or asthma),
• baclofen or dantrolene (infusion), both used to treat muscle stiffness in conditions such as multiple sclerosis; dantrolene is also used to treat malignant hyperthermia during anaesthesia (symptoms include very high fever and muscle rigidity),
• certain antibiotics such as rifampicin, erythromycin, clarithromycin (for bacterial infections),
• antiepileptic agents such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone,
• itraconazole, ketoconazole (medicines used to treat fungal infections),
• alpha-blockers used for the treatment of enlarged prostate such as prazosin, alfuzosin, doxazosin, tamsulosin, terazosin,
• amifostine (used to prevent or reduce side effects caused by other medicines or radiation therapy used in cancer treatment),
• corticosteroids (used to treat various conditions including severe asthma and rheumatoid arthritis),
• gold salts, particularly when administered intravenously (used to treat symptoms of rheumatoid arthritis),
• ritonavir, indinavir, nelfinavir (also called protease inhibitors used to treat HIV),
• tacrolimus (a medicine used to modify immune system function, allowing the body to accept transplanted organs),
• medicines usually used to treat diarrhoea (racecadotril) or to prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus, and other medicines belonging to the class of so-called mTOR inhibitors). See the section "Warnings and precautions".

Perindopril and amlodipine HCS with food and drink
Perindopril and amlodipine HCS should be taken before a meal.
Grapefruit and grapefruit juice must not be consumed by patients taking Perindopril and amlodipine HCS. This is because grapefruit and grapefruit juice may increase blood levels of the active substance amlodipine, which could cause an unpredictable increase in the blood pressure-lowering effect of Perindopril and amlodipine HCS.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
You must inform your doctor if you think you are (or may become) pregnant. Your doctor will normally advise you to stop taking Perindopril and amlodipine HCS before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine. Perindopril and amlodipine HCS is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used beyond the third month of pregnancy.
Breastfeeding
Inform your doctor if you are breastfeeding or about to start breastfeeding. Perindopril and amlodipine HCS is not recommended for breastfeeding mothers. If you wish to breastfeed, your doctor may choose an alternative treatment, especially if your baby is newborn or premature.

Driving and using machines
Perindopril and amlodipine HCS may affect your ability to drive and use machines. If the tablets cause you to feel unwell, dizzy, weak, or tired, do not drive or operate machinery and inform your doctor immediately.

3. How to take Perindopril and amlodipine HCS

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Swallow the tablet whole with a glass of water, preferably always at the same time of day, in the morning, before a meal. Your doctor will decide the correct dose for you. This is usually one tablet per day.
Perindopril and amlodipine HCS is usually prescribed for patients who are already taking perindopril and amlodipine as separate tablets.

If you take more Perindopril and amlodipine HCS than you should
If you take too many tablets, contact the nearest emergency department or inform your doctor immediately. The most likely symptoms of overdose are low blood pressure, which may make you feel dizzy or faint. If this happens, lying down with your legs raised may help.

If you forget to take Perindopril and amlodipine HCS
It is important that you take your medicine every day, as regular treatment works best. However, if you forget to take a dose of Perindopril and amlodipine HCS, take the next dose at your usual time.
Do not take a double dose to make up for the forgotten dose.

If you stop taking Perindopril and amlodipine HCS
Since treatment with Perindopril and amlodipine HCS is usually lifelong, you must discuss with your doctor before stopping your tablets.

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 gets them.
If you experience any of the following side effects, stop taking this medicine and inform your doctor immediately:

• sudden breathlessness, chest pain, shortness of breath or difficulty breathing
• swelling of the eyelids, face or lips
• swelling of the tongue and throat causing severe breathing difficulties
• severe skin reactions including intense rash, hives, redness of the skin all over the body, severe itching, blisters, skin peeling and swelling, mucosal inflammation (Stevens-Johnson syndrome) or other allergic reactions
• severe dizziness or fainting
• heart attack, irregular heartbeat
• inflammation of the pancreas which may cause severe abdominal and back pain accompanied by a general feeling of illness.

The following common side effects have been reported. If any of these cause you problems or last longer than one week, you should contact your doctor:

• Common side effects (may affect up to 1 in 10 people): headache, dizziness, drowsiness (especially at the beginning of treatment), vertigo, numbness or tingling sensations in the limbs, visual disturbances (including double vision), tinnitus (ringing or noises in the ears), palpitations (awareness of heartbeat), flushing, confusion due to low blood pressure, cough, shortness of breath, nausea (feeling unwell), vomiting (feeling sick), abdominal pain, taste disturbances, dyspepsia or indigestion, diarrhoea, constipation, allergic reactions (such as skin rashes, itching), muscle cramps, fatigue, weakness, swelling of the ankle (oedema).

Other reported side effects include the following. If any of these worsen, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist.

• Uncommon side effects (may affect up to 1 in 100 people): mood swings, anxiety, depression, insomnia, sleep disturbances, tremor, loss of pain sensation, rhinitis (blocked or runny nose), changes in bowel habits, hair loss, red spots on the skin, skin discoloration, back pain, muscle or joint pain, chest pain, difficulty urinating, increased need to urinate at night, increased frequency of urination, pain, discomfort, bronchospasm (tightness in the chest, wheezing and shortness of breath), dry mouth, angioedema (symptoms such as wheezing, swelling of the face or tongue), kidney problems, impotence, increased sweating, discomfort or breast enlargement in men, weight gain or weight loss.

• Rare side effects (may affect up to 1 in 1,000 people): confusion, worsening of psoriasis.

• Very rare side effects (may affect up to 1 in 10,000 people): cardiovascular disorders (irregular heartbeat, angina, heart attack and stroke), eosinophilic pneumonia (a rare type of pneumonia), swelling of the eyelids, face or lips, swelling of the tongue and throat causing severe breathing difficulties, severe skin reactions including intense rash, hives, redness of the skin all over the body, severe itching, blisters, skin peeling and swelling, mucosal inflammation (Stevens-Johnson syndrome), erythema multiforme (a skin rash that often starts with itchy spots on the face, arms or legs), light sensitivity, blood disorders, inflammation of the pancreas which may cause abdominal and back pain accompanied by a general feeling of illness, abnormal liver function, inflammation of the liver (hepatitis), yellowing of the skin (jaundice), increased liver enzymes which may affect certain clinical tests, abdominal swelling (gastritis), nerve disorders which may cause weakness, tingling or numbness, increased muscle tension, vasculitis (inflammation of blood vessels), gum swelling, excess sugar in the blood (hyperglycaemia).

• Side effects with unknown frequency (frequency cannot be estimated from the available data): tremor, rigid posture, mask-like facial expression (lack of expression), slow movements, and unbalanced, unstable gait.

The following side effects have also been reported in patients taking perindopril/amlodipine: hypoglycaemia (very low blood sugar levels), movement disorders combining rigidity, tremors and/or movement disturbances.

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 www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Perindopril and amlodipine HCS

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 pack after Exp. The expiry date refers to the last day of that month.
Store in the original packaging to protect from light and moisture.
This medicine does not require any special temperature storage conditions.
Do not dispose of medicines 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 Perindopril and Amlodipine HCS contains

• The active substances are perindopril tert-butylamine and amlodipine.
  Perindopril and Amlodipine HCS 4 mg/5 mg tablets
  Each tablet contains 4 mg of perindopril tert-butylamine (equivalent to 3.34 mg of perindopril) and 5 mg of amlodipine (as besylate).
  Perindopril and Amlodipine HCS 4 mg/10 mg tablets
  Each tablet contains 4 mg of perindopril tert-butylamine (equivalent to 3.34 mg of perindopril) and 10 mg of amlodipine (as besylate).
  Perindopril and Amlodipine HCS 8 mg/5 mg tablets
  Each tablet contains 8 mg of perindopril tert-butylamine (equivalent to 6.68 mg of perindopril) and 5 mg of amlodipine (as besylate).
  Perindopril and Amlodipine HCS 8 mg/10 mg tablets
  Each tablet contains 8 mg of perindopril tert-butylamine (equivalent to 6.68 mg of perindopril) and 10 mg of amlodipine (as besylate).

• The other components are sodium hydrogen carbonate, microcrystalline cellulose (E460), pregelatinized maize starch, sodium starch glycolate (type A), anhydrous colloidal silica and magnesium stearate (E572).

Description of the appearance of Perindopril and Amlodipine HCS and contents of the pack
Perindopril and Amlodipine HCS 4 mg/5 mg tablets
This medicinal product appears as white to almost white, round, slightly biconvex tablets with bevelled edges, engraved with the symbol U 1 on one side. Diameter: 7 mm.

Perindopril and Amlodipine HCS 4 mg/10 mg tablets
This medicinal product appears as white to almost white, capsule-shaped, biconvex tablets with bevelled edges and a score line on one side. The tablets are engraved with U on one side and marked with 2 on the other side of the score line. Dimensions: 12.5 mm x 5.5 mm. The score line is intended to facilitate swallowing and does not allow division into equal doses.

Perindopril and Amlodipine HCS 8 mg/5 mg tablets
This medicinal product appears as white to almost white, round, biconvex tablets with bevelled edges, engraved with the symbol U 3 on one side. Diameter: 9 mm.

Perindopril and Amlodipine HCS 8 mg/10 mg tablets
This medicinal product appears as white to almost white, round, biconvex tablets with bevelled edges and a score line on one side. The tablets are engraved with the symbol U on one side and marked with 4 on the other side of the score line. Diameter: 9 mm. The tablet can be divided into two equal doses.

The tablets are available in packs containing:

• 10, 30, 60, 90 and 100 tablets in blister packs,
• 10 x 1, 30 x 1, 60 x 1, 90 x 1 and 100 x 1 tablets in single-dose perforated blister packs.

Not all pack sizes may be marketed.

Marketing Authorization Holder
HCS bvba, H Kennisstraat 53, B 2650 Edegem, Belgium

Local representative in Italy:
KRKA Farmaceutici Milano S.r.l. – Italy

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

This medicinal product is authorized in the European Economic Area countries under the following names: