Ramladio

Package leaflet: Information for the patient

Ramladio, 5 mg + 5 mg, hard capsules
Ramladio, 5 mg + 10 mg, hard capsules
Ramladio, 10 mg + 5 mg, hard capsules
Ramladio, 10 mg + 10 mg, hard capsules
Ramiprilum + Amlodipinum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Ramladio is and what it is used for

Ramladio contains two active substances: ramipril and amlodipine. Ramipril belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors), while amlodipine belongs to a group of medicines called calcium antagonists.

Ramipril works by:

• reducing the production in the body of substances that may increase blood pressure,
• relaxing and widening blood vessels,
• helping the heart to pump blood throughout the body.

Amlodipine works by:

• relaxing and widening blood vessels, allowing blood to flow through them more easily.

Ramladio may be used in the treatment of high blood pressure (hypertension) in patients whose blood pressure has been adequately controlled using both active substances at the same doses as in the combination product, but administered as separate tablets.

2. Important information before using Ramladio

When not to use Ramladio:

• If the patient is allergic to ramipril, amlodipine (the active substances), other ACE inhibitors, other calcium antagonists, or any of the other ingredients of this medicine (listed in section 6). Symptoms of an allergic reaction may include: rash, difficulty swallowing or breathing, swelling of lips, face, throat or tongue, itching or redness of the skin.
• If the patient has ever experienced a severe allergic reaction called "angioedema". Symptoms include: itching, hives, red patches on hands, feet and throat, swelling of the throat and tongue, swelling around eyes and lips, difficulty breathing and swallowing.
• If the patient is undergoing dialysis or other type of blood filtration. Depending on the equipment used, treatment with Ramladio may not be suitable.
• If the patient has kidney disorders causing reduced blood flow to the kidneys (renal artery stenosis).
• During the last 6 months of pregnancy (see section below “Pregnancy and breastfeeding”).
• If the patient has abnormally low (hypotension) or unstable blood pressure – the physician will assess the patient's condition.
• If the patient has diabetes or kidney dysfunction and is being treated with a blood pressure-lowering medicine containing aliskiren.
• If the patient has aortic valve stenosis or is in cardiogenic shock (a condition in which the heart is unable to deliver sufficient blood to the body).
• If the patient has heart failure following a heart attack.
• If the patient has taken or is currently using sacubitril with valsartan, a medicine used to treat certain types of chronic (long-term) heart failure in adults, because the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) increases.

Do not use Ramladio if any of the above conditions apply to the patient.
If in doubt, consult a doctor before taking Ramladio.

Warnings and precautions

Before starting treatment with Ramladio, discuss it with your doctor or pharmacist.
Inform your doctor if the patient has or has had any of the following conditions:

• if the patient has heart, liver or kidney disorders;
• if there has been significant loss of electrolytes or fluids from the body [due to vomiting, diarrhoea, excessive sweating, low-salt diet, prolonged use of diuretics (water tablets) or dialysis];
• if desensitization treatment is planned to reduce allergy to bee or wasp venom;
• if anaesthesia is planned – both for surgical and dental procedures. It may be necessary to stop taking Ramladio one day before anaesthesia – consult your doctor;
• if the patient has high potassium levels in the blood (detected in a blood laboratory test);
• if the patient is taking medicines that reduce sodium levels in the blood or has conditions that may cause low sodium levels in the blood – your doctor may recommend regular blood tests to monitor blood sodium levels, especially in elderly patients;
• if the patient is pregnant, suspects or plans pregnancy. Use of Ramladio is not recommended during the first 3 months of pregnancy. This medicine may seriously harm the unborn child if used after the 3rd month of pregnancy (see section below “Pregnancy and breastfeeding”);
• if the patient has collagenosis, such as scleroderma or systemic lupus erythematosus;
• if the patient experiences a significant increase in blood pressure (hypertensive crisis);
• if the patient is elderly and requires dose escalation;
• if the patient is taking any of the following medicines used to treat high blood pressure:
• an angiotensin II receptor antagonist (AIIRA) (also known as sartans, e.g. valsartan, telmisartan, irbesartan), especially if the patient has kidney dysfunction related to diabetes;
• aliskiren.
• if the patient is taking any of the following medicines, which increase the risk of angioedema (rapid swelling of the skin in areas such as the throat):
• racecadotril, a medicine used to treat diarrhoea;
• medicines used to prevent rejection of transplanted organs and in cancer treatment (e.g. temsirolimus, sirolimus, everolimus);
• vildagliptin, a medicine used to treat diabetes.

Your doctor may recommend regular monitoring of kidney function, blood pressure, and blood electrolyte levels (e.g. potassium).

See also the section “When not to use Ramladio”.

• if the patient develops sudden swelling of the lips, face, tongue, throat, neck, or possibly hands and feet, difficulty swallowing or breathing, hives or hoarseness (angioedema). These may be symptoms of a severe allergic reaction, which may occur at any time during treatment. Patients of Black race may be at higher risk of developing angioedema. If such symptoms occur, contact a doctor immediately.

Children and adolescents

Ramladio is not recommended for use in children and adolescents under 18 years of age, as safety and efficacy have not been established in this age group.

Ramladio and other medicines

Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

Inform your doctor if you are taking any of the following medicines:

• medicines used to relieve pain and inflammation [e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as: ibuprofen, indomethacin or acetylsalicylic acid];
• medicines used for low blood pressure, shock, heart failure, asthma or allergies, such as: ephedrine, noradrenaline or adrenaline – your doctor will recommend monitoring of blood pressure;
• anticancer medicines (used in chemotherapy);
• medicines to prevent rejection of transplanted organs, such as cyclosporine;
• diuretics (water tablets), such as furosemide;
• medicines that may increase potassium levels in the blood, such as: spironolactone, triamterene, amiloride, potassium salts and heparin (used to thin the blood);
• corticosteroid anti-inflammatory medicines, such as prednisolone;
• allopurinol (used to reduce uric acid levels in the blood);
• procainamide (used for heart rhythm disorders);
• temsirolimus (used in the treatment of malignant tumours);
• vildagliptin (used in the treatment of type 2 diabetes);
• antidiabetic medicines, such as oral glucose-lowering agents and insulin. Ramladio may lower blood sugar levels. Blood glucose levels should be monitored regularly during treatment with Ramladio;
• lithium (used to treat psychiatric disorders). Ramladio may increase lithium levels in the blood. Your doctor will recommend regular monitoring of blood lithium levels;
• ketoconazole, itraconazole (used to treat fungal infections);
• ritonavir, indinavir, nelfinavir (so-called protease inhibitors used in the treatment of HIV infection);
• rifampicin, erythromycin, clarithromycin (antibiotics used to treat bacterial infections);
• St John's wort (Hypericum perforatum);
• verapamil, diltiazem (used to treat heart conditions and high blood pressure);
• dantrolene (used intravenously in severe temperature disorders);
• tacrolimus (used to control immune system response, allowing the body to accept a transplanted organ);
• simvastatin (a medicine that lowers blood cholesterol levels);
• medicines most commonly used to prevent rejection of transplanted organs (sirolimus, everolimus and other medicines belonging to the class of mTOR inhibitors). See section

“Warnings and precautions”.

• potassium supplements (including salt substitutes), potassium-sparing diuretics and other medicines that increase potassium levels in the blood (e.g. trimethoprim and co-trimoxazole, used in bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent rejection of transplanted organs; and heparin, a medicine used to thin the blood to prevent clots).

Your doctor may recommend dose adjustment and/or additional precautions:

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections “When not to use Ramladio” and “Warnings and precautions”).

If any of the above conditions apply to the patient (or if you have any doubts), talk to your doctor before using Ramladio.

Ramladio with food, drink and alcohol

Ramladio can be taken independently of meals.

Drinking alcohol while taking Ramladio may cause dizziness or a sensation of "emptiness" in the head. If in doubt about how much alcohol can be consumed while taking Ramladio, consult your doctor, as blood pressure-lowering medicines and alcohol may enhance each other's effects.

While taking Ramladio, do not drink grapefruit juice or eat grapefruits, as grapefruit and grapefruit juice may increase blood levels of the active substance – amlodipine – which could lead to an unexpected intensification of the blood pressure-lowering effect of Ramladio.

Pregnancy and breastfeeding

Pregnancy

Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning pregnancy.

Do not use Ramladio during the first 12 weeks of pregnancy and do not use it after week 13 of pregnancy, as its use may harm the unborn child.

Inform your doctor immediately if you become pregnant while taking Ramladio. If you are planning pregnancy, your doctor will recommend switching to another appropriate medicine.

Breast-feeding

Do not take Ramladio while breast-feeding.

It has been shown that small amounts of amlodipine pass into breast milk. Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Ramladio may impair the ability to drive and operate machinery. If the patient experiences nausea, dizziness, fatigue or headache, driving and operating machinery should be avoided and medical advice should be sought immediately. Adverse effects are more likely to occur at the beginning of treatment or when increasing the dose of Ramladio.

3. How to take Ramladio

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
The medicine should be taken orally, at the same time each day, before or after a meal.
Capsules should be swallowed whole with liquid.
Do not take Ramladio with grapefruit juice.
Ramladio should be taken once daily.
Elderly patients
The doctor may prescribe a lower starting dose and increase the dose more slowly.
Taking more than the recommended dose of Ramladio
Taking too high a dose of this medicine may cause low blood pressure, even dangerously low.
Dizziness, a feeling of "emptiness" in the head, fainting, or weakness may occur. In cases of severe
hypotension, shock may develop. The patient's skin becomes cold and clammy, and loss of
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4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If any of the following serious adverse effects occur, you must stop taking Ramladio and immediately contact a doctor – urgent medical care may be necessary:

• swelling of the face, lips or throat causing difficulty in swallowing or breathing, skin itching and rash. These may be symptoms of a severe allergic reaction to Ramladio.
• severe skin reactions, including: rash, mouth ulcers, worsening of pre-existing skin disease, redness, blistering or peeling of the skin, severe itching with blisters, skin peeling and swelling, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme).

Contact your doctor immediately if you experience:

• increased heart rate, irregular or forceful heartbeat (palpitations), chest pain, feeling of chest pressure or more serious disturbances, including heart attack or stroke;
• shortness of breath, cough, sudden wheezing, chest pain or difficulty breathing – these may be symptoms of lung disease;
• easier bruising, prolonged bleeding time, various types of bleeding (e.g. bleeding gums), red, pinpoint skin hemorrhages (petechiae), or increased susceptibility to infections, sore throat and fever, fatigue, fainting, dizziness or pale skin – these may be symptoms of blood or bone marrow disorders;
• severe upper abdominal pain radiating to the back – this may be a symptom of pancreatitis;
• fever, chills, fatigue, loss of appetite, stomach pain, nausea, yellowing of the skin or eyes (jaundice) – these may be symptoms of liver disorders such as hepatitis or liver damage;
• swelling of the eyelids or tongue;
• allergic reactions.

Adverse effects associated with ramipril:
Common (may occur in less than 1 in 10 patients):

• headache or feeling of fatigue
• dizziness – more likely at the beginning of treatment with Ramladio or after dose increase
• fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting down quickly
• dry, persistent cough, sinusitis or bronchitis, shortness of breath
• stomach or abdominal pain, diarrhea, indigestion, nausea or vomiting
• skin rash with or without raised lesions
• chest pain
• muscle cramps or pain
• increased potassium levels, detected in blood laboratory tests

Uncommon (may occur in less than 1 in 100 patients):

• balance disturbances (vestibular dizziness)
• itching and unusual sensory sensations such as numbness, tingling, pricking, burning or crawling sensations on the skin (paresthesia)
• loss or disturbances of taste
• sleep disturbances
• low mood, anxiety, increased nervousness or restlessness
• nasal congestion, breathing difficulties or worsening of asthma
• intestinal swelling, known as "intestinal angioedema", presenting as abdominal pain, vomiting and diarrhea
• heartburn, constipation or dryness of the oral mucosa
• increased urination during the day
• excessive sweating
• loss of or reduced appetite (anorexia)
• rapid or irregular heartbeat
• swelling of hands and feet, which may indicate increased fluid retention in the body
• sudden flushing, especially of the face
• blurred vision
• joint pain
• fever
• impotence, decreased libido in men or women
• increased number of certain white blood cells (eosinophilia), detected in blood laboratory tests
• disturbances in liver, pancreas or kidney function, detected in blood laboratory tests

Rare (may occur in less than 1 in 1,000 patients):

• feeling of uneasiness or disorientation
• redness and swelling of the tongue
• severe skin peeling or detachment, itchy nodular rash
• nail disorders (e.g. loosening or separation of the nail plate from the nail bed)
• skin rash or bruising
• skin spots and cold extremities
• redness, itching, swelling or watering of the eyes
• hearing disturbances and tinnitus
• feeling of weakness
• decreased number of red blood cells, white blood cells or platelets, or decreased hemoglobin concentration, detected in blood laboratory tests

Very rare (may occur in less than 1 in 10,000 patients):

• increased sensitivity to sunlight

Frequency not known (frequency cannot be estimated from available data):

• concentrated urine (dark-colored), nausea or vomiting, muscle cramps, confusion and seizures, which may result from inappropriate antidiuretic hormone (ADH) secretion – if such symptoms occur, contact your doctor immediately

Other reported adverse effects:
If any of the following adverse effects worsen or persist for longer than a few days, inform your doctor.

• concentration difficulties
• swelling of the oral mucosa
• decreased number of blood cells, detected in blood laboratory tests
• decreased sodium concentration in blood, detected in blood laboratory tests
• color change of fingers and toes after cold exposure, followed by tingling or pain upon warming (Raynaud's phenomenon)
• breast enlargement in men
• slowed or impaired reactions
• burning sensation
• smell disturbances
• hair loss

Adverse effects associated with amlodipine:
Very common (may occur in at least 1 in 10 patients):

• swelling around the ankles (edema)

Common (may occur in less than 1 in 10 patients):

• headache, dizziness, drowsiness (especially at the beginning of treatment)
• palpitations (sensation of strong heartbeat), sudden flushing, especially of the face
• abdominal pain, nausea
• changes in bowel habits, diarrhea, constipation, indigestion
• fatigue, weakness
• visual disturbances, double vision
• muscle cramps

Below are other reported adverse effects. If any of these adverse effects worsen or if any adverse effects not listed in this leaflet occur, inform your doctor or pharmacist.
Uncommon (may occur in less than 1 in 100 patients):

• mood changes, anxiety, depression, insomnia

• tremor, taste disturbances, fainting

• sensation of numbness or tingling in limbs, loss of pain sensation

• tinnitus

• low blood pressure

• sneezing or runny nose due to inflammation of the nasal mucosa (rhinitis)

• cough

• dryness of the oral mucosa, vomiting

• hair loss, increased sweating, skin itching, red skin spots, skin discoloration

• urinary disturbances, increased need to urinate at night, increased frequency of urination

• inability to achieve erection, discomfort or breast enlargement in men

• pain, malaise

• joint or muscle pain, back pain

• increase or decrease in body weight

Rare (may occur in less than 1 in 1,000 patients):

• disorientation

Very rare (may occur in less than 1 in 10,000 patients):

• decreased number of white blood cells, decreased number of platelets, which may lead to easy bruising and bleeding
• increased blood glucose levels (hyperglycemia)
• nerve disorders causing weakness, tingling or numbness sensations
• gum swelling
• abdominal bloating (gastritis)
• liver function disturbances, hepatitis, yellowing of the skin (jaundice), increased liver enzyme activity, detected in laboratory tests
• increased muscle tone
• vasculitis, often with skin rash
• photosensitivity
• movement disorders involving stiffness, tremor and/or difficulty moving

Frequency not known (frequency cannot be estimated from available data):

• tremor, postural rigidity, facial masking, slowed movements and shuffling gait, unsteady walking.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Ramladio

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton and blister. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Store in the original packaging to protect from light and moisture.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What the medicine Ramladio contains

• The active substances are ramipril and amlodipine (as amlodipine besilate).
  5 mg + 5 mg: each hard capsule contains 5 mg of ramipril and 5 mg of amlodipine (as amlodipine besilate).
  5 mg + 10 mg: each hard capsule contains 5 mg of ramipril and 10 mg of amlodipine (as amlodipine besilate).
  10 mg + 5 mg: each hard capsule contains 10 mg of ramipril and 5 mg of amlodipine (as amlodipine besilate).
  10 mg + 10 mg: each hard capsule contains 10 mg of ramipril and 10 mg of amlodipine (as amlodipine besilate).
• Other ingredients (capsule content): hypromellose 6 cP, pregelatinized corn starch, microcrystalline cellulose, magnesium stearate.
  Other ingredients (capsule shell):
• 5 mg + 5 mg and 10 mg + 5 mg: titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172), gelatin, black ink [shellac (E 904), propylene glycol, potassium hydroxide, black iron oxide (E 172)].
• 5 mg + 10 mg: titanium dioxide (E 171), red iron oxide (E 172), gelatin, black ink [shellac (E 904), propylene glycol, potassium hydroxide, black iron oxide (E 172)].
• 10 mg + 10 mg: titanium dioxide (E 171), red iron oxide (E 172), gelatin, white ink [shellac (E 904), propylene glycol, potassium hydroxide, titanium dioxide (E 171)].

What Ramladio looks like and contents of the pack
Ramladio 5 mg + 5 mg, hard capsules:
The capsule body is orange-brown with a black imprint "0505". The cap is orange-brown. The capsule contains a white to almost white powder, possibly with crystals. Capsule size No. 2.

Ramladio 5 mg + 10 mg, hard capsules:
The capsule body is white to almost white with a grey to black imprint "0510". The cap is brown-red. The capsule contains a white to almost white powder, possibly with crystals. Capsule size No. 0.

Ramladio 10 mg + 5 mg, hard capsules:
The capsule body is white to almost white with a grey to black imprint "1005". The cap is orange-brown. The capsule contains a white to almost white powder, possibly with crystals. Capsule size No. 0.

Ramladio 10 mg + 10 mg, hard capsules:
The capsule body is brown-red with a white imprint "1010". The cap is brown-red. The capsule contains a white to almost white powder, possibly with crystals. Capsule size No. 0.

Packaging:

• 30, 50, 60, 90 and 100 hard capsules in blister packs in a cardboard box,
• 30 x 1, 50 x 1, 60 x 1, 90 x 1 and 100 x 1 hard capsules in unit dose blisters in a cardboard box. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Krka, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
For more detailed information on the names of medicinal products in other European Economic Area countries, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
Równoległa Street 5
02-235 Warsaw, Poland
Tel. 22 57 37 500