Ramlolan

Package leaflet: Information for the patient

Ramlolan, 2.5 mg + 5 mg, hard capsules
Ramlolan, 5 mg + 5 mg, hard capsules
Ramlolan, 5 mg + 10 mg, hard capsules
Ramlolan, 10 mg + 5 mg, hard capsules
Ramlolan, 10 mg + 10 mg, hard capsules
Ramiprilum + Amlodipinum
Please read carefully this leaflet before using the medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, 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.

Table of contents

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

1. What Ramlolan is and what it is used for

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

The action of ramipril consists of:

• Reducing the production in the body of substances that may increase blood pressure
• Relaxing and widening blood vessels
• Making it easier for the heart to pump blood throughout the body

The action of amlodipine consists of:

• Relaxing and widening blood vessels, which facilitates blood flow through them.

Ramlolan is used for the treatment of hypertension (high blood pressure) in adult patients whose blood pressure is adequately controlled with a combination of ramipril and amlodipine at the same doses as those contained in Ramlolan, but administered as separate preparations.

2. Information before using Ramlolan

When not to use Ramlolan:

• If the patient is allergic to ramipril, amlodipine (the active substances), other drugs in the class of ACE inhibitors, or any other drugs in the class of calcium antagonists, or to any of the other ingredients of this medicine (listed in section 6). Symptoms of an allergic reaction may include: swelling, redness of the skin, or difficulty breathing.
• If the patient has ever experienced a severe allergic reaction called "angioedema". Symptoms include: swelling, urticaria (hives), red patches 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 taking or currently uses 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.
• If the patient is undergoing dialysis or another type of blood filtration. Depending on the type of equipment used, Ramlolan may not be suitable for the patient.
• If the patient has kidney diseases associated with reduced blood flow to the kidneys (renal artery stenosis).
• During the last 6 months of pregnancy (see below, section "Pregnancy, breastfeeding and fertility").
• If the patient has diabetes or kidney impairment and is being treated with a blood pressure-lowering medicine containing aliskiren.
• If blood pressure is very low or unstable. The doctor will monitor blood pressure.
• If the patient has aortic valve stenosis (narrowing of the aorta) or cardiogenic shock (a condition in which the heart is unable to deliver sufficient blood to the body).
• If the patient has been diagnosed with heart failure following myocardial infarction.

If any of the above situations apply to the patient, Ramlolan must not be used. In case of doubt, consult a doctor before taking Ramlolan.

Warnings and precautions

Before starting treatment with Ramlolan, discuss this with your doctor, pharmacist, or nurse. Inform your doctor if any of the following situations apply to you:

• If the patient has heart, liver, or kidney diseases.
• If the patient has recently lost a significant amount of electrolytes or fluids (due to vomiting, diarrhoea, excessive sweating, a low-salt diet, prolonged use of diuretics (water tablets), or dialysis).
• If the patient is due to undergo treatment to reduce allergic reactions to bee or wasp venom (desensitisation).
• If the patient is due to undergo anaesthesia. This may be related to a surgical or dental procedure. It may be necessary to stop taking Ramlolan one day before the procedure; contact your doctor for advice.
• If the patient has high levels of potassium in the blood (as shown in blood test results).
• If the patient has been diagnosed with a collagen disease such as scleroderma or systemic lupus erythematosus.
• If the patient is taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor antagonist (ARB) (also known as sartans – for example, valsartan, telmisartan, irbesartan), especially if the patient has kidney impairment related to diabetes.
  • aliskiren. The treating doctor may monitor kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals. See also information under the heading "When not to use Ramlolan".
• If the patient has been diagnosed with a significant increase in blood pressure (hypertensive crisis). If dose increase is necessary in elderly patients.
• If the patient develops a persistent dry cough.
• If blood pressure is not sufficiently lowered. Medicines in this class are likely to be less effective in black patients.
• If the patient is taking any of the following medicines, the risk of angioedema may increase:
  • 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.

If the patient experiences sudden swelling of the lips and face, tongue and throat, neck, and sometimes also hands and feet, difficulty swallowing or breathing, hives, or hoarseness ("angioedema"), these may be symptoms of a severe allergic reaction. Such a reaction may occur at any time during treatment, and the risk is higher in black patients. If such symptoms occur, inform your doctor immediately.

Children and adolescents

Ramlolan is not recommended for use in children and adolescents under 18 years of age due to lack of data in this population.

Ramlolan with other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

Inform your doctor if you are taking any of the following medicines. These medicines may reduce the effectiveness of Ramlolan:

• Medicines used to relieve pain and for anti-inflammatory purposes (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, indomethacin, or aspirin).
• Medicines used to treat low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. The doctor will monitor blood pressure.
• Rifampicin (an antibiotic used to treat tuberculosis).
• St John's wort (used to treat depression).

Inform your doctor if you are taking any of the following medicines. They may increase the risk of adverse effects when taken together with Ramlolan:

• Erythromycin, clarithromycin (antibiotics).
• Temsirolimus (used to treat malignant tumours) and other medicines used in cancer treatment (chemotherapy).
• Medicines most commonly used to prevent rejection of transplanted organs (sirolimus, everolimus, and other drugs belonging to the class of mTOR inhibitors); see section "Warnings and precautions".
• Tacrolimus (used to control the immune system response, allowing the body to accept a transplanted organ).
• Medicines used to relieve pain and for anti-inflammatory purposes (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, indomethacin, or acetylsalicylic acid).
• Diuretics (water tablets), such as furosemide.
• 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 for 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).
• Steroidal anti-inflammatory medicines, such as prednisolone.
• Allopurinol (a medicine used to reduce uric acid levels in the blood).
• Procainamide (a medicine used for heart rhythm disorders).
• Ketoconazole, itraconazole (antifungal medicines).
• Ritonavir, indinavir, nelfinavir (so-called protease inhibitors used in the treatment of HIV infection).
• Verapamil, diltiazem (medicines used to treat heart rhythm disorders or high blood pressure).
• Dantrolene (a medicine administered by infusion in severe body temperature disorders).

The treating doctor may need to adjust the dose and/or take other precautions:

• If the patient is taking an angiotensin II receptor antagonist (ARB) or aliskiren (see also information under the headings "When not to use Ramlolan" and "Warnings and precautions").

Inform your doctor if you are taking any of the following medicines. Ramlolan may affect their action:

• Vildagliptin and other medicines used in diabetes, such as oral antidiabetic medicines and insulin. Ramlolan may reduce blood glucose levels. Blood glucose levels should be carefully monitored during treatment with Ramlolan.
• Lithium (a medicine used in psychiatric disorders). Ramlolan may cause increased lithium levels in the blood. The doctor will closely monitor lithium levels in the patient.
• Simvastatin (a medicine that reduces cholesterol levels). Ramlolan may cause increased simvastatin levels in the blood.

If the patient is taking any of the medicines listed above (or is unsure about this), they should consult their doctor before taking Ramlolan.

Taking Ramlolan with food, drink, and alcohol

Ramlolan can be taken with or without food.

Drinking alcohol while taking Ramlolan may cause dizziness or a feeling of lightheadedness. If in doubt about the amount of alcohol allowed while taking Ramlolan, consult your doctor, as the effects of blood pressure-lowering medicines and alcohol are additive.

Patients taking Ramlolan should not consume grapefruit or grapefruit juice. This is because grapefruit and grapefruit juice may increase blood levels of the active substance amlodipine, which could lead to unpredictable intensification of the blood pressure-lowering effect of Ramlolan.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.

Pregnancy

Ramlolan must not be used during pregnancy. If pregnancy occurs while taking Ramlolan, inform your doctor immediately. If planning pregnancy, the doctor will switch to an appropriate alternative treatment.

Breastfeeding

Ramlolan must not be used during breastfeeding. Before taking any medicine, consult your doctor or pharmacist.

Fertility

There is insufficient data on the potential effect of the medicine on fertility.

Driving and using machines

Ramlolan may affect the ability to drive or operate machinery. If Ramlolan causes nausea, dizziness, fatigue, or headache, the patient should not drive or operate machinery and should contact their doctor immediately. These symptoms may occur especially at the beginning of treatment or when changing medicines.

Ramlolan contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per capsule, meaning the medicine is considered "sodium-free".

3. How to take Ramlolan

This medicine should always be taken exactly as directed by the physician or pharmacist. In case of doubt,
consult your doctor or pharmacist.
If you feel that the effect of Ramlolan is too strong or too weak, consult your doctor or pharmacist.
This medicine should be taken orally, at the same time each day, either before or after a meal.
The capsule should be swallowed whole with liquid.
Do not take Ramlolan with grapefruit juice.
Ramlolan should be taken once daily.
Your doctor may adjust the dose depending on your response to the medicine.
The maximum recommended daily dose is one 10 mg + 10 mg capsule.

Elderly patients
Your doctor will use a lower initial dose and adjust the dose more gradually.

Patients with kidney and/or liver impairment
Dosage adjustments may be necessary in patients with liver or kidney problems.

Use in children and adolescents
Ramlolan is not recommended for use in children and adolescents under 18 years of age due to lack of data in this population.

Taking more Ramlolan than recommended
Taking too many capsules may cause a drop in blood pressure, even to dangerously low levels. The patient may then experience dizziness, lightheadedness, or weakness; fainting may also occur. In cases of severe hypotension, shock may develop—characterized by cold, clammy skin and loss of consciousness.
If an overdose is suspected, contact your doctor immediately or go to the emergency department of the nearest hospital. The patient must not drive to the hospital—ask someone else for help or call emergency services. Bring the medicine packaging with you. This will help the doctor identify which medicine has been taken.
Shortness of breath caused by fluid accumulation in the lungs (pulmonary edema) may occur up to 24–48 hours after taking the medicine.

Missed dose of Ramlolan
If you miss a dose, do not take the missed dose. Take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

Stopping treatment with Ramlolan
Your doctor will advise you on the duration of treatment. Do not stop taking Ramlolan without consulting your doctor, as this may lead to a recurrence of the illness.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine may cause adverse reactions, although they do not occur in everyone.
If any of the following serious adverse reactions occur, discontinue taking Ramlolan and contact your doctor immediately – urgent medical assistance may be required:

• Swelling of the face, lips or throat, making swallowing or breathing difficult, as well as itching and rash. These may be symptoms of a severe allergic reaction to Ramlolan.
• Severe skin reactions, including rash, mouth ulcers, worsening of existing skin diseases, redness, blistering or peeling of the skin (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme) or other allergic reactions. The frequency of occurrence of the above-mentioned adverse reactions is unknown (cannot be estimated from available data).

Promptly inform your doctor if any of the following symptoms occur:

• Increased heart activity, irregular or stronger heartbeat (palpitations), chest pain, chest tightness or more severe disturbances, including myocardial infarction and stroke. These adverse reactions occur frequently (chest pain, chest tightness, palpitations) or uncommonly (increased heart rate, myocardial infarction or stroke).
• Shortness of breath or cough. These are common adverse reactions which may be symptoms of lung diseases.
• Easy bruising, prolonged bleeding time, any signs of bleeding (e.g. bleeding gums), purple skin spots, petechiae or more frequent infections than usual, sore throat and fever, feeling of fatigue, fainting, dizziness or pale skin. These may be symptoms of blood or bone marrow disorders. These are rare adverse reactions.
• Severe upper abdominal pain which may radiate to the back. This may be a symptom of pancreatitis. This is an uncommon adverse reaction.
• Fever, chills, malaise, loss of appetite, stomach pain, nausea, yellowing of the skin or whites of the eyes (jaundice). These may be symptoms of liver disorders, such as hepatitis or liver damage. The frequency of occurrence of these adverse reactions is unknown (cannot be estimated from available data).

Other adverse reactions:
Inform your doctor if any of the following symptoms worsen or persist for more than a few days.
Common adverse reactions (may occur in less than 1 in 10 people):

• Drowsiness (especially at the beginning of treatment)
• Palpitations (awareness of heartbeat), sudden flushing (especially of the face)
• Swelling around the ankles
• Headache or feeling of fatigue
• Dizziness; risk of occurrence is higher at the beginning of treatment with Ramlolan or after dose increase
• Fainting, hypotension (abnormally low blood pressure), especially when standing up or sitting down quickly from a lying position
• Dry, persistent cough, sinusitis or bronchitis, shortness of breath
• Abdominal pain, stomach or intestinal pain, diarrhoea, indigestion, nausea or vomiting
• Skin rash, with or without raised lesions
• Chest pain
• Muscle cramps or pain
• Increased potassium levels in blood (detected in blood tests).

Uncommon adverse reactions (may occur in less than 1 in 100 people):

• Myocardial infarction
• Mood swings, insomnia
• Tremor, weakness, pain, malaise
• Visual disturbances, double vision, blurred vision, tinnitus
• Sneezing/runny nose due to inflammation of the nasal mucosa (rhinitis)
• Changes in bowel habits (including diarrhoea or constipation), heartburn, dryness of the oral mucosa
• Hair loss, increased sweating, skin itching, red skin spots, skin discoloration
• Urinary disturbances, increased need to urinate, especially at night, increased frequency of urination
• Inability to achieve erection, impotence in men, decreased libido in men and women
• Discomfort or enlargement of breasts in men
• Joint or muscle pain, muscle cramps, back pain
• Increase or decrease in body weight
• Balance disturbances (dizziness)
• Skin itching and unusual skin sensations such as tingling, numbness, pricking, burning or stinging (paresthesia), loss of pain sensation
• Loss or disturbances of taste sensation
• Sleep disturbances
• Depression, anxiety, increased nervousness or restlessness
• Nasal congestion, breathing difficulties or worsening of asthma
• Intestinal swelling described as "angioedema of the intestine", with symptoms such as abdominal pain, vomiting and diarrhoea
• Loss or decrease in appetite (anorexia)
• Rapid or irregular heartbeat
• Swelling of the upper and lower limbs, possibly indicating fluid retention
• Fever
• Increased number of a certain type of white blood cells (eosinophilia), detected in blood tests
• Liver, pancreas or kidney function disorders, detected in blood tests.

Rare adverse reactions (may occur in less than 1 in 1000 people):

• Feeling of unsteadiness or confusion
• Redness and swelling of the tongue
• Severe skin peeling, itchy nodular rash
• Nail disorders (e.g. loosening or separation of the nail from the nail bed)
• Skin rash or bruising
• Urticaria
• Skin spots and cold extremities
• Redness, itching, swelling or watering of the eyes
• Hearing disturbances
• Decreased number of red blood cells, white blood cells or platelets, or hemoglobin concentration, detected in blood tests

Very rare adverse reactions (may occur in less than 1 in 10,000 people):

• Photosensitivity
• Increased blood glucose levels (hyperglycemia)
• Swelling of the gums
• Abdominal bloating (inflammation of the gastric mucosa)
• Liver function disorders, hepatitis, jaundice (yellowing of the skin)
• Increased muscle tension
• Vasculitis, often accompanied by skin rash
• Photosensitivity
• Disorder involving rigidity, tremor and/or movement disturbances

Adverse reactions with unknown frequency (frequency cannot be estimated from available data):

• Concentrated urine (dark in color), nausea or vomiting, muscle cramps, confusion and seizures, which may result from inappropriate ADH (antidiuretic hormone – vasopressin) secretion. If the above symptoms occur, contact your doctor immediately

• Tremor, postural rigidity, facial masking, slowed movements and shuffling gait

Other observed adverse reactions:
Inform your doctor if any of the following symptoms worsen or persist for more than a few days.

• Difficulty concentrating
• Decreased number of blood cells, detected in blood tests
• Decreased sodium levels in blood, detected in blood tests
• Color change in fingers and toes due to cold, followed by tingling or pain upon warming (Raynaud's phenomenon)
• Slowed or impaired reactions
• Taste disturbances
• Psoriasis.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of 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 reactions can also be reported to the marketing authorization holder.
Reporting of adverse reactions helps to gather more information on the safety of the medicine.

5. How to store Ramlolan

Keep this medicine out of sight and reach of children.
Store below 30°C.
Keep in the original packaging to protect from light.
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 the stated month.
Medicines should not be disposed of 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 Ramlolan contains

• The active substances are:
  2.5 mg + 5 mg, hard capsules: each capsule contains 2.5 mg ramipril and 5 mg amlodipine as amlodipine besylate.
  5 mg + 5 mg, hard capsules: each capsule contains 5 mg ramipril and 5 mg amlodipine as amlodipine besylate.
  5 mg + 10 mg, hard capsules: each capsule contains 5 mg ramipril and 10 mg amlodipine as amlodipine besylate.
  10 mg + 5 mg, hard capsules: each capsule contains 10 mg ramipril and 5 mg amlodipine as amlodipine besylate.
  10 mg + 10 mg, hard capsules: each capsule contains 10 mg ramipril and 10 mg amlodipine as amlodipine besylate.

• Other components are: microcrystalline cellulose, calcium hydrogen phosphate, pregelatinized corn starch, sodium carboxymethyl starch (type A), sodium stearyl fumarate, iron oxide red (E 172), titanium dioxide (E 171), gelatin.
  Additionally for the 10 mg + 10 mg strength: iron oxide yellow (E 172), iron oxide black (E 172).
  Black ink: shellac, iron oxide black (E 172), propylene glycol, ammonium hydroxide.

What Ramlolan looks like and contents of the pack
Ramlolan 2.5 mg + 5 mg, hard capsules: Hard gelatin capsules, size no. 1 (19.1–19.7 mm), cap: opaque, light pink colour; body: opaque, white colour with black print “R 2.5 mg A 5 mg”. Capsule contents: white or almost white powder.
Ramlolan 5 mg + 5 mg, hard capsules: Hard gelatin capsules, size no. 1 (19.1–19.7 mm), cap: opaque, pink colour; body: opaque, white colour with black print “R 5 mg A 5 mg”. Capsule contents: white or almost white powder.
Ramlolan 5 mg + 10 mg, hard capsules: Hard gelatin capsules, size no. 1 (19.1–19.7 mm), cap: opaque, reddish-brown colour; body: opaque, white colour with black print “R 5 mg A 10 mg”. Capsule contents: white or almost white powder.
Ramlolan 10 mg + 5 mg, hard capsules: Hard gelatin capsules, size no. 1 (19.1–19.7 mm), cap: opaque, dark pink colour; body: opaque, white colour with black print “R 10 mg A 5 mg”. Capsule contents: white or almost white powder.
Ramlolan 10 mg + 10 mg, hard capsules: Hard gelatin capsules, size no. 1 (19.1–19.7 mm), cap: opaque, brown colour; body: opaque, white colour with black print “R 10 mg A 10 mg”. Capsule contents: white or almost white powder.

Ramlolan is available in packs containing 28, 30, 32, 56, 60, 90, 91, 96, 98 or 100 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
G.L. Pharma GmbH
Schlossplatz 1
8502 Lannach
Austria

Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Poland

This medicinal product is authorised in the EEA Member States under the following names:
Austria: Ramlolan 2.5 mg/5 mg-Hartkapseln
Ramlolan 5 mg/5 mg-Hartkapseln
Ramlolan 5 mg/10 mg-Hartkapseln
Ramlolan 10 mg/5 mg-Hartkapseln
Ramlolan 10 mg/10 mg-Hartkapseln
Poland: Ramlolan

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
G.L. PHARMA POLAND Sp. z o.o.
Al. Jana Pawła II 61/313
01-031 Warsaw, Poland
Tel: 022/ 636 52 23; 636 53 02
[email protected]