Aproxxamlo

Patient Information Leaflet

Aproxxamlo 150 mg/5 mg film-coated tablets, 150 mg/10 mg film-coated tablets, 300 mg/5 mg film-coated tablets, 300 mg/10 mg film-coated tablets

irbesartan/amlodipine
Read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Aproxxamlo is and what it is used for

What Aproxxamlo is
Aproxxamlo contains two active substances: irbesartan and amlodipine.
What Aproxxamlo is used for
Aproxxamlo is used to treat arterial hypertension in adults who are already taking
irbesartan and amlodipine as separate tablets.
How Aproxxamlo works
Irbesartan belongs to a group of medicines known as “angiotensin-II receptor antagonists”. Angiotensin-II is a substance produced in the body and causes narrowing of blood vessels, thereby increasing blood pressure. Irbesartan works by blocking the effect of angiotensin-II, resulting in relaxation of blood vessels, which in turn reduces blood pressure.
Amlodipine belongs to a group of substances called “calcium antagonists”. Amlodipine prevents calcium from entering the walls of blood vessels, causing relaxation of the blood vessels and thereby reducing blood pressure.
This means that both of these substances help prevent the narrowing of blood vessels. As a result, blood vessels relax and blood pressure is lowered.

2. What you need to know before taking Aproxxamlo

Do not take Aproxxamlo:

• if you are allergic to irbesartan, amlodipine, any other calcium antagonist, or to any of the other ingredients of this medicine (listed in section 6).
• if you have narrowing of the heart's aortic valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body).
• if you have heart failure following a heart attack.
• if you have particularly low blood pressure (hypotension).
• if you are more than 3 months pregnant (see section “Pregnancy and breastfeeding”).
• if you have diabetes or kidney problems and are being treated with a medicine containing aliskiren that lowers blood pressure.

Warnings and precautions
Talk to your doctor before taking Aproxxamlo if you are in any of the following conditions:

• excessive vomiting or diarrhoea: this may lead to excessive loss of fluids and/or salts in the body
• severely impaired liver function
• kidney problems
• narrowing or blockage of blood vessels
• heart problems
• diabetic kidney disorders
• you are taking medicines for high blood pressure called:
• ACE inhibitors, for example enalapril, lisinopril, ramipril, particularly if you have diabetes-related kidney problems
• aliskiren.

Your doctor may check your kidney function, blood pressure, and levels of electrolytes (such as potassium) in your blood at regular intervals.

• signs of a severe increase in blood pressure (hypertensive crisis)
• if you develop low blood sugar levels (symptoms may include sweating, weakness, hunger, dizziness, trembling, headache, flushing or paleness, numbness, rapid and pounding heartbeat), especially if you are being treated for diabetes. Contact your doctor if you suspect you are pregnant (or might become pregnant). Aproxxamlo is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the baby if taken during this period (see section 2 “Pregnancy and breastfeeding”). This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially “sodium-free”.

See also the information provided in the section “Do not take Aproxxamlo”.
Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age, as safety and efficacy have not been established.
Other medicines and Aproxxamlo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Aproxxamlo may interact with or be affected by other medicines, such as:

• ACE inhibitors or aliskiren (see also “Do not take Aproxxamlo” and “Warnings and precautions”)
• diuretics, including potassium-sparing diuretics (also called “water tablets” that increase the amount of urine produced), or limited salt intake, which may lead to extreme loss of fluids and salts in the body
• potassium supplements, potassium-containing salt substitutes, and other substances that may increase potassium levels
• lithium, a medicine used to treat certain types of depression
• certain types of painkillers or medicines that reduce inflammation called “non-steroidal anti-inflammatory drugs” (NSAIDs) or “selective cyclooxygenase-2 inhibitors” (COX-2 inhibitors), as these may cause progressive worsening of kidney function
• antiepileptic agents (medicines used for epilepsy), such as carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone
• St. John’s wort (also known as “hypericum perforatum”), an herbal medicine used for depression
• nitroglycerin and other nitrates or other medicines called “vasodilators” (medicines that cause blood vessels to widen)
• medicines used for HIV/AIDS – such as ritonavir, indinavir, nelfinavir
• medicines used to treat fungal infections, such as ketoconazole, itraconazole
• medicines used to treat bacterial infections, such as rifampicin, erythromycin, clarithromycin
• heart medicines, such as verapamil, diltiazem
• medicine used to control high cholesterol levels (simvastatin)
• infusion of dantrolene, a medicine used to treat a rare reaction to anaesthesia in which body temperature rises extremely rapidly (malignant hyperthermia)
• medicines used to prevent transplant rejection (cyclosporine)
• medicines used to modify the immune system function, such as tacrolimus, sirolimus, temsirolimus, and everolimus
• repaglinide (a medicine used to lower blood sugar levels).

Aproxxamlo with food and drink
Aproxxamlo can be taken with or without food.
Do not drink grapefruit juice or eat grapefruit while taking Aproxxamlo. This is because grapefruit and grapefruit juice can increase the amount of the active ingredient, amlodipine, in the blood. This may unpredictably lower your blood pressure.
Pregnancy and breastfeeding
Pregnancy
Do not take Aproxxamlo if you are pregnant.
If you suspect or are planning a pregnancy, your doctor will normally advise you to stop taking Aproxxamlo and to switch to another medicine. This is because Aproxxamlo is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the unborn baby.
If you suspect or are planning a pregnancy, consult your doctor before taking this medicine.
Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor will normally advise you to stop taking Aproxxamlo before and during breastfeeding and will recommend another medicine instead of Aproxxamlo, especially if the baby is a newborn or was born prematurely.
Driving and using machines
Aproxxamlo may affect your ability to drive or operate machinery. If the tablets make you feel unwell, dizzy, tired, or cause headache, do not drive or operate machinery and contact your doctor immediately.

3. How to take Aproxxamlo

Take this medicine exactly as your doctor has instructed you. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the appropriate dose of Aproxxamlo based on your condition and whether you are taking other medicines.
It is important to continue taking Aproxxamlo for the entire duration prescribed by your doctor in order to maintain stable blood pressure control.

Taking the medicine
Aproxxamlo tablets are for oral use.
The recommended dose is one tablet per day. Try to take your daily dose at the same time each day.
Take the tablets with a sufficient amount of liquid, such as a glass of water. Do not take Aproxxamlo with grapefruit or grapefruit juice.
You may take Aproxxamlo with or without food.

Children and adolescents
Do not give Aproxxamlo to children and adolescents under 18 years of age.

If you take more Aproxxamlo than you should
If you accidentally take too many tablets, contact your doctor immediately. Symptoms of overdose include low blood pressure, increased heart rate, or possibly reduced heart rate.

If you forget to take Aproxxamlo
If you accidentally forget to take a dose, take the next dose as usual. Do not take a double dose to make up for the missed dose.

If you have any questions about the use of 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.

Serious side effects
Stop treatment with Aproxxamlo and contact your doctor immediately or go to the nearest hospital emergency department if you experience any of the following serious side effects:

• severe allergic reaction, with symptoms such as rash, itching, swelling of the face, lips, mouth or throat, which may cause difficulty in swallowing or breathing, anaphylactic shock (frequency not known)
• severe skin reactions, including severe rash, hives, redness of the skin all over the body, intense itching, blisters, skin peeling and swelling, inflammation of mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis) (frequency not known)
• heart attack (may affect up to 1 in 10,000 people)
• inflammation of the pancreas, which may cause severe abdominal and back pain and make you feel very unwell (may affect up to 1 in 10,000 people)

Other side effects
The following side effects have been reported with irbesartan and/or amlodipine:

Very common (may affect more than 1 in 10 people)

• blood tests may show increased potassium levels in case of hypertension and type 2 diabetes with kidney disease
• oedema (fluid retention)

Common (may affect up to 1 in 10 people)

• dizziness, orthostatic dizziness (when moving from a sitting or lying position to standing), headache, fatigue, weakness, drowsiness
• visual disturbances (including double vision)
• fast or irregular heartbeat
• redness and feeling of warmth in the face and/or neck
• shortness of breath or difficulty breathing
• abdominal pain, nausea or vomiting
• changes in bowel habits, diarrhoea, constipation, indigestion
• muscle cramps

Uncommon (may affect less than 1 in 100 people)

• mood changes, depression, anxiety, insomnia
• tremor, taste disturbances, fainting
• tingling or numbness in the hands or feet, loss of pain sensitivity
• ringing in the ears
• low blood pressure
• sneezing or runny nose due to inflammation of the nasal mucosa (rhinitis)
• cough
• dry mouth
• hair loss, excessive sweating
• itchy skin, red spots on the skin, changes in skin pigmentation, rash
• joint or muscle pain, back pain
• urinary problems, increased need to urinate at night, increased frequency of urination
• yellowing of the skin (jaundice)
• inability to achieve or maintain an erection, discomfort or enlargement of the breasts in men, sexual dysfunction
• pain, chest pain, feeling unwell
• weight gain or weight loss

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

• confusion

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

• decrease in white blood cell count, decrease in blood platelets which may cause unusual bruising or easy bleeding
• high blood sugar (hyperglycaemia)
• swollen gums
• abdominal swelling (gastritis)
• abnormal liver function, inflammation of the liver (hepatitis), increased liver enzymes which may affect certain medical tests
• unusual muscle stiffness
• numbness or weakness in arms and legs
• inflammation of blood vessels, often with rash
• light sensitivity

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

• impaired kidney function
• severe skin reaction starting with painful red areas, followed by large blisters and ending with peeling of skin layers. This is accompanied by fever and chills, muscle pain and generally feeling unwell
• low blood sugar levels
• decrease in red blood cell count (anaemia – symptoms may include fatigue, headache, shortness of breath during physical activity, dizziness and paleness)

If any of the above side effects becomes severe, inform your doctor.

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 Aproxxamlo

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.
Do not store above 30 °C.
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 Aproxxamlo contains
The active substances are irbesartan and amlodipine.

• Each film-coated tablet of Aproxxamlo 150 mg/5 mg contains 150 mg of irbesartan and 5 mg of amlodipine (as amlodipine besilate).
• Each film-coated tablet of Aproxxamlo 300 mg/10 mg contains 300 mg of irbesartan and 10 mg of amlodipine (as amlodipine besilate).
• The other components are:
  Tablet core: sodium croscarmellose, hypromellose, magnesium stearate, microcrystalline cellulose and anhydrous colloidal silica
  Film coating: hypromellose, macrogol, titanium dioxide (E171).
• Each film-coated tablet of Aproxxamlo 150 mg/10 mg contains 150 mg of irbesartan and 10 mg of amlodipine (as amlodipine besilate).
• The other components are:
  Tablet core: sodium croscarmellose, hypromellose, magnesium stearate, microcrystalline cellulose and anhydrous colloidal silica
  Film coating: hypromellose, macrogol, titanium dioxide (E171) and red iron oxide (E172).
• Each film-coated tablet of Aproxxamlo 300 mg/5 mg contains 300 mg of irbesartan and 5 mg of amlodipine (as amlodipine besilate).
• The other components are:
  Tablet core: sodium croscarmellose, hypromellose, magnesium stearate, microcrystalline cellulose and anhydrous colloidal silica
  Film coating: hypromellose, macrogol, titanium dioxide (E171) and yellow iron oxide (E172).

Description of the appearance of Aproxxamlo and package contents
Aproxxamlo 150 mg/5 mg film-coated tablets are white, oval-shaped, with the numbers “150/5” engraved on one side.
Aproxxamlo 150 mg/10 mg film-coated tablets are pink, oval-shaped, with the numbers “150/10” engraved on one side.
Aproxxamlo 300 mg/5 mg film-coated tablets are yellow, oval-shaped, with the numbers “300/5” engraved on one side.
Aproxxamlo 300 mg/10 mg film-coated tablets are white, oval-shaped, with a breakline on one side.

Aproxxamlo film-coated tablets are supplied in blisters containing 15, 28, 30, 90 or 98 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Sanofi S.r.l.
Viale L. Bodio, 37/B
20158 Milan, Italy

Manufacturer:
S.C. Zentiva, S.A.
B-dul Theodor Pallady nr.50, sector 3, Bucharest, cod 032266
Romania

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Spain: APROXXAMLO 150 mg/5 mg film-coated tablets; APROXXAMLO 150 mg/10 mg film-coated tablets; APROXXAMLO 300 mg/5 mg film-coated tablets; APROXXAMLO 300 mg/10 mg film-coated tablets
Greece, Italy, Portugal: APROXXAMLO
Belgium, Luxembourg: Aprexevo 150 mg/5 mg filmomhulde tabletten – comprimés pelliculés – Filmtabletten; Aprexevo 150 mg/10 mg filmomhulde tabletten – comprimés pelliculés – Filmtabletten; Aprexevo 300 mg/5 mg filmomhulde tabletten – comprimés pelliculés – Filmtabletten; Aprexevo 300 mg/10 mg filmomhulde tabletten – comprimés pelliculés – Filmtabletten
France, Romania: APREXEVO