Ramladio

Leaflet accompanying the packaging: patient information

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

Ramipril + Amlodipine

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Ramladio and what is it 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 packaging and other information

1. What is Ramladio and what is it 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 can increase blood pressure,
• relaxing and dilating blood vessels,
• making it easier for the heart to pump blood throughout the body.

Amlodipine works by:

• relaxing and dilating blood vessels, making it easier for blood to flow through them.

Ramladio can be used to treat high blood pressure (hypertension) in patients who have achieved adequate blood pressure control when taking both active substances separately in the same doses as in the combination medicine.

2. Important information before taking Ramladio

When not to take Ramladio:

• If the patient is allergic to ramipril, amlodipine (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 the lips, face, throat, or tongue, itching or redness of the skin.
• If the patient has ever had a severe allergic reaction called "angioedema". Its symptoms include: itching, hives, red spots on the hands, feet, and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing.
• If the patient is undergoing dialysis or other blood filtration treatment. Depending on the device used, treatment with Ramladio may not be suitable.
• If the patient has kidney problems that reduce blood flow to the kidneys (renal artery stenosis).
• During the last 6 months of pregnancy (see below "Pregnancy and breastfeeding").
• If the patient has abnormally low (hypotension) or unstable blood pressure - the doctor will assess the patient's condition.
• If the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren.
• If the patient has a narrowing of the aortic valve or is in cardiogenic shock (a condition in which the heart is unable to supply the body with enough blood).
• If the patient has heart failure after a heart attack.
• If the patient has taken or is currently taking sacubitril/valsartan, a medicine used to treat a certain type of chronic (long-term) heart failure in adults, as the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) increases.

If any of the above conditions apply to the patient, Ramladio should not be taken.
In case of doubt, the patient should consult a doctor before taking Ramladio.

Warnings and precautions

Before starting to take Ramladio, the patient should discuss it with their doctor or pharmacist.
The patient should inform their doctor if they have or have had any of the following conditions:

• heart, liver, or kidney problems;
• significant loss of electrolytes or fluids from the body [due to vomiting, diarrhea, excessive sweating, low-salt diet, prolonged use of diuretics (diuretics) or dialysis];
• planned desensitization treatment to reduce allergy to bee or wasp venom;
• planned anesthesia - both for surgical and dental procedures. It may be necessary to stop taking Ramladio the day before anesthesia - the patient should consult their doctor;
• high potassium levels in the blood (detected in a blood test);
• taking medicines that lower sodium levels in the blood or having conditions that may lower sodium levels in the blood - the doctor may recommend regular blood tests to measure sodium levels in the blood, especially in elderly patients;
• if the patient is pregnant, suspects or plans to become pregnant. Ramladio should not be taken during the first 3 months of pregnancy. This medicine may seriously harm the baby if taken after the 3rd month of pregnancy (see below "Pregnancy and breastfeeding");
• if the patient has collagenosis, such as scleroderma or systemic lupus erythematosus;
• if the patient has a significant increase in blood pressure (hypertensive crisis);
• if the patient is elderly and requires a dose increase;
• if the patient is taking any of the following medicines used to treat high blood pressure:
• angiotensin II receptor antagonist (AIIRA) (also called sartan, e.g., valsartan, telmisartan, irbesartan), especially if the patient has kidney problems related to diabetes;
• aliskiren.
• if the patient is taking any of the following medicines, which increase the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat):
• racecadotril, a medicine used to treat diarrhea;
• medicines used to prevent organ rejection and to treat cancer (e.g., temsirolimus, sirolimus, everolimus);
• sildagliptin, a medicine used to treat type 2 diabetes.

The doctor may recommend regular assessment of kidney function, blood pressure, and electrolyte levels (e.g., potassium) in the blood.
See also the subsection "When not to take Ramladio".

• if the patient experiences sudden swelling of the lips, face, tongue, and throat, neck, or hands and feet, difficulty swallowing or breathing, hives, or hoarseness (angioedema). These may be symptoms of a severe allergic reaction that can occur at any time during treatment. Black patients may be more likely to experience angioedema. If such symptoms occur, the patient should contact their doctor immediately.

Children and adolescents

Ramladio should not be taken by children and adolescents under 18 years of age, as the safety and efficacy of this medicine in this age group have not been established.

Ramladio and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
The patient should tell their doctor about 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 to treat low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, norepinephrine, or adrenaline - the doctor will recommend blood pressure monitoring;
• anticancer medicines (used in chemotherapy);
• medicines used to prevent organ rejection, such as cyclosporine;
• diuretics (diuretics), such as furosemide;
• medicines that can 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 to treat heart rhythm disorders);
• temsirolimus (used to treat cancer);
• sildagliptin (used to treat type 2 diabetes);
• antidiabetic medicines, such as oral glucose-lowering medicines and insulin. Ramladio may lower blood sugar levels. During treatment with Ramladio, the patient should regularly check their blood sugar levels;
• lithium (used to treat mental disorders). Ramladio may increase lithium levels in the blood. The doctor will recommend regular monitoring of lithium levels in the blood;
• ketokonazole, itraconazole (used to treat fungal infections);
• ritonavir, indinavir, nelfinavir (protease inhibitors used to treat HIV infection);
• rifampicin, erythromycin, clarithromycin (antibiotics used to treat bacterial infections);
• St. John's Wort (Hypericum perforatum);
• verapamil, diltiazem (used to treat heart diseases and high blood pressure);
• dantrolene (used in infusion for severe body temperature disorders);
• tacrolimus (used to control the immune system, allowing the body to accept a transplanted organ);
• simvastatin (a medicine that lowers cholesterol levels in the blood);
• medicines commonly used to prevent organ rejection (sirolimus, everolimus, and other medicines belonging to the class of mTOR inhibitors). See section "Warnings and precautions".

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 cotrimoxazole, used to treat bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ rejection, and heparin, a medicine used to thin the blood to prevent blood clots).

The doctor may recommend a dose change and/or take other precautions:

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also subsections "When not to take Ramladio" and "Warnings and precautions").

If any of the above conditions apply to the patient (or in case of any doubts), before taking Ramladio, the patient should consult their doctor.

Ramladio with food, drink, and alcohol

Ramladio can be taken with or without food.
Drinking alcohol while taking Ramladio may cause dizziness or a feeling of "emptiness" in the head. In case of doubt about the amount of alcohol that can be consumed while taking Ramladio, the patient should consult their doctor, as blood pressure-lowering medicines and alcohol can enhance each other's effects.
While taking Ramladio, the patient should not drink grapefruit juice or eat grapefruits, as grapefruits and grapefruit juice can lead to increased levels of the active substance amlodipine in the blood, which can cause unexpected enhancement of the blood pressure-lowering effect of Ramladio.

Pregnancy and breastfeeding

Pregnancy
The patient should inform their doctor about pregnancy, suspected or planned pregnancy.
Ramladio should not be taken during the first 12 weeks of pregnancy and should not be taken after the 13th week of pregnancy, as it may harm the baby.
The patient should immediately tell their doctor if they become pregnant while taking Ramladio. If the patient is planning to become pregnant, the doctor will recommend taking a different, suitable medicine.
Breastfeeding
Ramladio should not be taken during breastfeeding.
It has been shown that small amounts of amlodipine pass into the breast milk of breastfeeding women. The patient should consult their doctor or pharmacist before taking any medicine.

Driving and operating machinery

Ramladio may impair the ability to drive and operate machinery. If the patient experiences nausea, dizziness, fatigue, or headache, they should not drive or operate machinery and should contact their doctor immediately. The occurrence of side effects is more likely when starting treatment or increasing the dose of Ramladio.

3. How to take Ramladio

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. In case of doubt, the patient should consult their doctor or pharmacist.
The medicine should be taken orally, once a day, at the same time, before or after a meal.
The capsules should be swallowed whole with a drink of water.
Ramladio should not be taken with grapefruit juice.
Ramladio should be taken once a day.
Elderly patients
The doctor will recommend a lower initial dose and will increase the dose more slowly.

Taking a higher dose of Ramladio than recommended

Taking too much of the medicine may cause a drop in blood pressure, and even dangerously low blood pressure. The patient may experience dizziness, a feeling of "emptiness" in the head, fainting, or weakness. In the case of a very significant drop in blood pressure, shock may occur. The patient's skin will become cool and moist, and they may lose consciousness.
In case of taking too much of Ramladio, the patient should immediately contact their doctor or go to the emergency department of the nearest hospital. The patient should not drive a car to the hospital, but should ask someone to drive them or call an ambulance. The patient should take the medicine packaging with them, so that the doctor knows which medicine was taken.
Even 24-48 hours after taking the medicine, shortness of breath due to excess fluid accumulating in the lungs (pulmonary edema) may occur.

Missing a dose of Ramladio

If the patient forgets to take a capsule, they should skip that dose and take the next dose at the usual time. The patient should not take a double dose to make up for the missed dose.

Stopping treatment with Ramladio

The doctor will determine how long the patient should take this medicine. If the patient stops taking the medicine earlier than recommended by the doctor, the disease may return.
In case of any further doubts about taking this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Ramladio can cause side effects, although not everybody gets them.
If any of the following serious side effects occur, the patient should stop taking Ramladio and immediately consult their doctor- emergency medical attention may be necessary:

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

The patient should immediately inform their doctor if they experience:

• rapid heartbeat, irregular or strong heartbeat (palpitations), chest pain, feeling of pressure in the chest, or more serious disorders, including heart attack or stroke;
• shortness of breath, cough, sudden wheezing, chest pain, or difficulty breathing - these may be symptoms of lung disease;
• easy bruising, prolonged bleeding, bleeding of various types (e.g., bleeding from the gums), red, spotty rash on the skin, or increased tendency to infections, sore throat, and fever, feeling of tiredness, fainting, dizziness, or paleness of the skin - these may be symptoms of blood or bone marrow disorders;
• severe abdominal pain that may radiate 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.

Side effects related to ramipril:
Common(may affect up to 1 in 10 people):

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

Uncommon(may affect up to 1 in 100 people):

• balance disorders (dizziness of labyrinthine origin)
• itching and abnormal sensations, such as numbness, tingling, prickling, or burning of the skin (paresthesia)
• loss or disturbance of taste
• sleep disorders
• depression, anxiety, increased nervousness, or restlessness
• nasal congestion, difficulty breathing, or worsening of asthma
• intestinal edema, called "angioedema of the intestine", manifested by abdominal pain, vomiting, and diarrhea
• heartburn, constipation, or dryness of the mucous membranes of the mouth
• increased urination during the day
• excessive sweating
• loss or decreased appetite (anorexia)
• rapid or irregular heartbeat
• swelling of the hands and feet, which may be a sign of water retention in the body
• sudden reddening, especially of the face
• blurred vision
• joint pain
• fever
• impotence, decreased libido in men or women
• increased white blood cell count, detected in blood tests
• liver, pancreas, or kidney function disorders, detected in blood tests

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

• feeling of uncertainty or disorientation
• redness and swelling of the tongue
• severe peeling or detachment of the skin, itchy rash with blisters
• nail disorders (e.g., loosening or separation of the nail plate from the nail bed)
• skin rash or bruising
• spots on the skin and cold extremities
• redness, itching, swelling, or tearing of the eyes
• hearing or ringing in the ears
• feeling of weakness
• decreased red blood cell, white blood cell, or platelet count, or decreased hemoglobin levels, detected in blood tests

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

• sensitivity to sunlight

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

• concentrated urine (dark-colored), nausea, or vomiting, muscle cramps, feeling of confusion, and seizures, which may be due to abnormal secretion of antidiuretic hormone (ADH) - if such symptoms occur, the patient should immediately consult their doctor

Other reported side effects:

If any of the following side effects worsen or persist for more than a few days, the patient should tell their doctor.

• concentration disorders
• swelling of the mucous membranes of the mouth
• decreased blood cell count, detected in blood tests
• decreased sodium levels in the blood, detected in blood tests
• change in finger and toe color after freezing, followed by tingling or pain after warming (Raynaud's phenomenon)
• breast enlargement in men
• slowed or impaired reactions
• burning sensation
• smell disorders
• hair loss

Side effects related to amlodipine:
Very common(may affect more than 1 in 10 people):

• swelling of the ankle area (edema)

Common(may affect up to 1 in 10 people):

• headache, dizziness, drowsiness (especially at the beginning of treatment)
• palpitations (feeling of strong heartbeat), sudden reddening, especially of the face
• abdominal pain, nausea
• change in bowel movements, diarrhea, constipation, indigestion
• fatigue, weakness
• vision disorders, double vision
• muscle cramps

The following are other reported side effects. If any of these side effects worsen or if any side effects not listed in this leaflet occur, the patient should inform their doctor or pharmacist.
Uncommon(may affect up to 1 in 100 people):

• mood changes, anxiety, depression, insomnia
• tremors, taste disorders, fainting
• feeling of numbness or tingling of the limbs, lack of pain sensation
• ringing in the ears
• low blood pressure
• rhinitis (inflammation of the nasal mucous membranes) or cough
• dryness of the mucous membranes of the mouth, vomiting
• hair loss, increased sweating, itching of the skin, red spots on the skin,

skin discoloration

• urination disorders, increased need to urinate at night, frequent urination
• impotence, discomfort, or breast enlargement in men
• pain, malaise
• joint or muscle pain, back pain
• weight gain or loss

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

• disorientation

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

• decreased white blood cell count, decreased platelet count, which can lead to easy bruising and bleeding
• increased blood sugar levels (hyperglycemia)
• nerve disorders that can cause weakness, numbness, or tingling
• gum swelling
• abdominal bloating (gastritis)
• liver function disorders, hepatitis, jaundice, increased liver enzyme activity, detected in blood tests
• increased muscle tone
• blood vessel inflammation, often with skin rash
• sensitivity to light
• disorders including stiffness, tremors, and/or difficulty moving

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

• tremors, stiffness, mask-like face, slow movements, and shuffling gait.

Reporting side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Jerozolimskie Avenue 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Ramladio

The medicine should be stored out of sight and reach of children.
Ramladio should not be taken after the expiry date stated on the carton and blister. The expiry date refers to the last day of the month.
The medicine should not be stored at temperatures above 30°C.
The medicine should be stored in its original packaging to protect it from light and moisture.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Ramladio contains

• The active substances of Ramladio are ramipril and amlodipine (in the form of amlodipine besylate). 5 mg + 5 mg: each hard capsule contains 5 mg of ramipril and 5 mg of amlodipine (in the form of amlodipine besylate). 5 mg + 10 mg: each hard capsule contains 5 mg of ramipril and 10 mg of amlodipine (in the form of amlodipine besylate). 10 mg + 5 mg: each hard capsule contains 10 mg of ramipril and 5 mg of amlodipine (in the form of amlodipine besylate). 10 mg + 10 mg: each hard capsule contains 10 mg of ramipril and 10 mg of amlodipine (in the form of amlodipine besylate).
• Other ingredients (capsule contents): hypromellose 6cP, cornstarch, 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 (capsules):
The body of the capsule is orange-brown with black printing 0505. The cap of the capsule is orange-brown. The capsule contains white or almost white powder, with possible crystals. Capsule size 2.
Ramladio, 5 mg + 10 mg, hard capsules (capsules):
The body of the capsule is white or almost white with gray to black printing 0510. The cap of the capsule is reddish-brown. The capsule contains white or almost white powder, with possible crystals. Capsule size 0.
Ramladio, 10 mg + 5 mg, hard capsules (capsules):
The body of the capsule is white or almost white with gray to black printing 1005. The cap of the capsule is orange-brown. The capsule contains white or almost white powder, with possible crystals. Capsule size 0.
Ramladio, 10 mg + 10 mg, hard capsules (capsules):
The body of the capsule is reddish-brown with white printing 1010. The cap of the capsule is reddish-brown. The capsule contains white or almost white powder, with possible crystals. Capsule size 0.

Packaging:

• 30, 50, 60, 90, and 100 hard capsules in blisters in a carton box,
• 30 x 1, 50 x 1, 60 x 1, 90 x 1, and 100 x 1 hard capsules in single-dose blisters in a carton box. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Krka, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
To obtain more detailed information on the names of medicinal products in other European Economic Area member states, the patient should contact the local representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5
02-235 Warsaw
Phone: 22 57 37 500
Date of last revision of the leaflet:01.07.2024