Icomb

Patient Information Leaflet: Information for the User

Icomb 5 mg/5 mg hard capsules, 5 mg/10 mg hard capsules, 10 mg/5 mg hard capsules, 10 mg/10 mg hard capsules

ramipril / amlodipine
Please 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 others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

1. What Icomb hard capsules (hereafter "Icomb") are and what they are used for
2. What you need to know before taking Icomb
3. How to take Icomb
4. Possible side effects
5. How to store Icomb
6. Contents of the pack and other information

1. What Icomb is and what it is used for

Icomb contains two active substances called ramipril and amlodipine. Ramipril belongs to a group of
medicines known as ACE inhibitors (Angiotensin-Converting Enzyme inhibitors), while
amlodipine belongs to a group of medicines called calcium channel blockers.
Ramipril works in the following ways:

• reduces the body's production of substances that could raise blood pressure
• relaxes and widens blood vessels
• makes it easier for the heart to pump blood around the body.

Amlodipine works in the following way:

• relaxes and widens blood vessels, allowing blood to flow through them more easily. Icomb can be used to treat high blood pressure (hypertension) in patients who are adequately controlled with the individual components administered simultaneously as separate tablets, at the same dosage levels as those present in the combination.

2. What you need to know before taking Icomb

Do not take Icomb

• If you are allergic to ramipril or amlodipine, or to any other calcium channel blocker or ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction may include rash, difficulty swallowing or breathing, and swelling of the lips, face, throat, or tongue.
• If you have severe 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 previously experienced a severe allergic reaction called "angioedema." Symptoms include itching, hives, red spots on hands, feet, and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing.
• If you are undergoing dialysis or any other type of blood filtration. Depending on the type of machine used, treatment with Icomb may not be suitable for you.
• If you have kidney problems due to reduced blood flow to the kidneys (renal artery stenosis).
• During the last 6 months of pregnancy (see the section below on "Pregnancy, breastfeeding and fertility").
• If your blood pressure is abnormally low or unstable. Your doctor will need to assess this.
• If you suffer from heart failure following a heart attack.
• If you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
• If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin, for example in the throat).

Do not take Icomb if any of the above conditions apply to you. If you are in doubt, consult your doctor before taking Icomb.

Warnings and precautions

Talk to your doctor or pharmacist before taking Icomb.

You must inform your doctor if you have or have had any of the following conditions:

• If you are elderly.
• If you have heart, liver, or kidney problems.
• If you experience a significant increase in blood pressure (hypertensive crisis).
• If you are at risk of developing circulatory problems in the heart or brain due to acute low blood pressure.
• If your body has lost significant amounts of salts or fluids (due to vomiting, diarrhoea, excessive sweating, salt restriction in diet, long-term use of diuretics (water tablets), or if undergoing dialysis).
• If you are scheduled to receive treatment to reduce allergy to bee or wasp stings (desensitisation).
• If you are to receive anaesthesia. This may be administered during surgery or dental procedures. You may need to stop taking Icomb the day before; consult your doctor for advice.
• If you have high levels of potassium in your blood (as indicated in blood test results).
• If you are taking medicines or have a condition that could lead to reduced sodium levels in your blood. Your doctor may require periodic blood tests, especially to monitor blood sodium levels, particularly if you are elderly.
• If you have a collagen-vascular disease such as scleroderma or systemic lupus erythematosus.
• If you have a cough. Inform your doctor if you notice worsening.
• If you are taking any of the following medicines used to treat high blood pressure:
  • an "angiotensin II receptor antagonist" (AIIRA) (also known as sartans – for example, valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes.
  • aliskiren. Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g. potassium) in your blood at regular intervals. See also the section "Do not take Icomb".
• If you are taking any of the following medicines, the risk of angioedema may increase:
  • racecadotril, a medicine used to treat diarrhoea.
  • medicines used to prevent organ transplant rejection and for cancer (e.g. temsirolimus, sirolimus, everolimus).
  • vildagliptin, a medicine used to treat diabetes.

You must inform your doctor if you think you are (or might become) pregnant. Icomb is not recommended during the first 3 months of pregnancy and may cause severe harm to the unborn child after the 3rd month of pregnancy (see section "Pregnancy, breastfeeding and fertility").

If any of the above conditions apply to you (or if you are in doubt), consult your doctor before taking Icomb.

Your doctor should monitor your white blood cell count. More frequent monitoring is advised:

• At the start of treatment.
• In patients with reduced kidney function or collagen vascular diseases.
• When medicines that affect blood cell counts are being used.

Children and adolescents

The use of Icomb should be avoided in children and adolescents under 18 years of age due to lack of data on safety and efficacy.

Other medicines and Icomb

See also the section "Do not take Icomb".

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Your doctor may consider it necessary to adjust the dose and/or take additional precautions:

If you are taking an angiotensin II receptor blocker (AIIRA) or aliskiren (see also sections "Do not take Icomb" and "Warnings and precautions").

The following medicines may reduce the effect of Icomb:

• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indometacin, acetylsalicylic acid).
• Medicines used to treat blood pressure, shock, heart failure, asthma, or allergies such as ephedrine, noradrenaline or adrenaline, isoprenaline, dobutamine or dopamine. Your doctor will need to monitor your blood pressure.
• Rifampicin (an antibiotic used to treat tuberculosis).
• Hypericum perforatum (St. John's wort – a herbal remedy for depression).

Inform your doctor if you are taking any of the following medicines. These may increase the likelihood of experiencing side effects when taken together with Icomb:

• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indometacin, acetylsalicylic acid).
• Medicines for cancer (chemotherapy).
• Medicines to prevent organ transplant rejection such as ciclosporin.
• Diuretics (water tablets) such as furosemide.
• Medicines that may increase potassium levels in the blood such as spironolactone, triamterene, amiloride, potassium salts, and heparin (to thin the blood).
• Steroid medicines for inflammation such as prednisolone.
• Allopurinol (used to lower uric acid in the blood).
• Procainamide (for heart rhythm problems).
• Ketoconazole, itraconazole (used to treat fungal infections).
• Erythromycin, clarithromycin (antibiotics used to treat certain bacterial infections).
• Ritonavir, indinavir, nelfinavir (protease inhibitors used to treat HIV).
• Verapamil, diltiazem (for treating certain heart conditions and high blood pressure).
• Dantrolene (infusion for severe body temperature abnormalities).
• Sirolimus (to prevent kidney transplant rejection).
• Trimethoprim and cotrimoxazole, also known as trimethoprim/sulfamethoxazole (for bacterial infections).
• Temsirolimus (for cancer).
• Everolimus (to prevent organ transplant rejection).
• Tacrolimus (used to control immune response, allowing the body to accept a transplanted organ).
• Racecadotril (used to treat diarrhoea).
• Vildagliptin (used to treat diabetes).
• Sacubitril/valsartan (used to treat heart problems). Do not take Icomb if you have taken or are currently taking sacubitril/valsartan (see section "Do not take Icomb").

The effect of the following medicines may be altered by Icomb:

• Medicines for diabetes such as oral glucose-lowering medicines and insulin. Icomb may lower blood sugar levels. Monitor your blood glucose levels carefully while taking Icomb.
• Lithium (for mental health conditions): Icomb may increase lithium levels in the blood. Your doctor must closely monitor your lithium levels.
• Simvastatin (a medicine to lower cholesterol): Amlodipine increases exposure to simvastatin. If you are taking Icomb, your doctor will need to reduce the dose of simvastatin.
• Ciclosporin (a medicine used to prevent organ transplant rejection).

If any of the above situations apply to you (or if you are uncertain), consult your doctor before taking Icomb.

Icomb with food, drinks and alcohol

• Grapefruit or grapefruit juice must not be consumed by people taking Icomb. This is because grapefruit or grapefruit juice may increase blood levels of the active ingredient amlodipine, which could enhance the blood pressure-lowering effect of Icomb.
• Drinking alcohol during treatment with Icomb may cause dizziness or drowsiness. If you are concerned about how much alcohol you can drink while taking Icomb, discuss this with your doctor, as blood pressure-lowering medicines and alcohol may intensify each other's sedative effects.

Pregnancy, breastfeeding and fertility

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy

You should not take Icomb during the first 12 weeks of pregnancy and must not take Icomb after the 13th week, as its use during pregnancy may harm the unborn child.

If you become pregnant while taking Icomb, inform your doctor immediately.

Switching to an appropriate alternative treatment should be considered before planning a pregnancy.

Breastfeeding

You must not take Icomb if you are breastfeeding.

Consult your doctor or pharmacist before taking any medicine.

Fertility

There are insufficient data on potential effects on fertility.

Driving and using machines

Icomb may affect your ability to drive or operate machinery. If the medicine causes nausea, dizziness, fatigue, or headache, do not drive or operate machinery and contact your doctor immediately.

Icomb 5 mg/5 mg capsules and 10 mg/5 mg capsules contain Allura Red AC-FD&C Red 40 (E129) and Icomb 5 mg/10 mg capsules and 10 mg/10 mg capsules contain azorubine, carmoisine (E122).

These colouring agents may cause allergic reactions.

3. How to take Icomb

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended dose is 1 capsule daily, at the strength prescribed by your doctor.
Depending on the effect, your doctor may adjust the dose.
The maximum dose is 1 capsule once daily of the 10 mg/10 mg strength.
Take this medicine by mouth at the same time each day, before or after a meal.
Swallow the hard capsule whole with a liquid.
Do not crush or chew the hard capsule.
Do not take Icomb with grapefruit juice.

Liver and kidney disease
Dosage may be adjusted in patients with liver or kidney disease.

Elderly
Your doctor may reduce the initial dose and adjust your treatment more gradually.
Administration of Icomb capsules should be avoided in very elderly and frail patients.

Use in children and adolescents
Icomb should not be used in children and adolescents under 18 years of age due to lack of data on safety and efficacy.

If you take more Icomb than you should
Taking too many capsules may cause a drop in blood pressure, or even a dangerous drop. This may lead to dizziness, lightheadedness, fainting, or a feeling of weakness. If the drop in blood pressure is severe enough, shock may occur. The skin may become cold and clammy and the person may lose consciousness. Seek immediate medical attention if you take too much Icomb. Do not drive to the hospital; have someone drive you or call an ambulance. Bring the medicine pack with you so the doctor knows what you have taken.
Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may develop up to 24–48 hours after ingestion.

If you forget to take Icomb
If you forget to take a capsule, skip that dose completely. Take the next dose at the usual time. Do not take a double dose to make up for a missed dose.

If you stop taking Icomb
Your doctor will advise you on how long to take this medicine. Your condition may return if you stop taking the medicine before advised.

If you have any questions about how to use 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.
Stop treatment with Icomb and contact your doctor immediately if you notice any of the following serious
side effects – you may need urgent medical treatment:

• Chest pain or tightness that may spread from the chest to the arms and may be accompanied by dizziness and shortness of breath. These may be signs of a heart attack, which has an uncommon frequency (may affect up to 1 in 100 people).
• Sudden and severe stomach pain, which may be accompanied by malaise. These may be signs of pancreatitis, which has an uncommon frequency (may affect up to 1 in 100 people).
• Swelling of the face, lips, or throat that may make swallowing or breathing difficult and may also be accompanied by an itchy rash. These may be signs of angioedema, which has an uncommon frequency (may affect up to 1 in 100 people).
• Severe skin reactions, including skin rashes, mouth ulcers, blistering or peeling of the skin (such as Stevens-Johnson syndrome or erythema multiforme), which have a very rare frequency (may affect up to 1 in 10,000 people). The reported frequency for toxic epidermal necrolysis is unknown.

Other side effects include:
Very common: may affect more than 1 in 10 people

• Edema (fluid retention)

Common: may affect up to 1 in 10 people

• Blood tests showing higher than normal levels of potassium in the blood
• Headache
• Dizziness
• Drowsiness
• Fainting
• Irregular or rapid heartbeat
• Unusually low blood pressure
• Unusually low blood pressure when standing up or sitting down quickly
• Flushing, redness
• Visual disturbances (including double vision)
• Dry cough and throat irritation
• Inflammation and irritation of the main airways of the lungs
• Inflammation of the sinuses (nasal cavities)
• Difficulty breathing
• Inflammation or irritation of the stomach or intestine
• Digestive disorders
• Abdominal discomfort
• Indigestion
• Diarrhea
• Nausea
• Vomiting
• Stomach ache
• Changes in bowel habits
• Constipation
• Rash
• Muscle cramps
• Muscle pain
• Chest pain
• Feeling of fatigue
• Swelling of limbs, including swelling of the ankles

Uncommon: may affect up to 1 in 100 people

• Increase in certain white blood cells shown in blood tests
• Loss or decrease in appetite (anorexia)
• Feeling depressed
• Mood changes, including anxiety
• Feeling more nervous than usual
• Feeling restless
• Difficulty sleeping
• Dizziness
• Tingling, prickling, or burning sensations
• Loss or alteration of taste
• Reduced sensitivity
• Tremor or restlessness
• Visual disturbances (including blurred vision)
• Ringing in the ears
• Increased heart rate
• Irregular heartbeat
• Sneezing/itchy nose/runny nose
• Cough
• Breathing difficulties or worsening of asthma
• Blood tests showing changes in pancreatic function
• Swelling in the intestine called "intestinal angioedema" presenting with symptoms such as abdominal pain, nausea, vomiting, and diarrhea
• Inflammation of the stomach
• Dry mouth
• Blood tests showing changes in liver function
• Red or purple spots or patches on the skin or lining of the mouth
• Discoloration of the skin
• Itching
• Hair loss
• Increased sweating
• Joint pain
• Back pain
• Decreased kidney function, including changes in frequency and/or volume of urine
• Problems urinating
• Increased need to urinate, especially at night
• Increased urine volume or need to urinate more frequently than usual during the day
• Blood or urine tests showing worsening of kidney function
• Inability to achieve or maintain an erection
• Reduced sexual desire in men or women
• Breast enlargement in men
• Fever
• Feeling of weakness or lack of energy
• Pain
• Feeling unwell
• Weight gain or loss
• Swelling of hands or legs/feet

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

• Blood tests showing a decrease in red blood cells, white blood cells, platelets, or hemoglobin levels
• Confusion
• Balance problems
• Red, itchy and/or swollen eyes
• Hearing problems
• Constriction of blood vessels
• Reduced blood flow
• Inflammation of blood vessels
• Red and swollen tongue
• Yellowing of the skin
• Liver damage/inflammation
• Peeling, delamination, and exfoliation of the skin, which may be accompanied by itching, redness, and hair loss
• Hives
• Nail problems (e.g., loosening or separation of the nail from the nail bed)

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

• Allergic reactions including sneezing, red itchy rash, watery eyes, itchy eyes, tightness in the chest, and shortness of breath
• Excess sugar in the blood
• Muscle stiffness, tremors and/or movement disorders
• Sensation of weakness, numbness, and pain, usually in hands and feet
• Enlargement of gum tissue
• Increased sensitivity to sunlight

Not known: frequency cannot be estimated from available data

• Blood tests indicating that the immune system may be overactive
• Bone marrow does not produce enough blood cells or platelets
• Blood tests showing insufficient numbers of blood cells
• The body retains too much water. You may have concentrated urine (dark-colored urine), feel unwell or become ill, experience muscle cramps, confusion, and seizures, which may be due to inadequate secretion of ADH (antidiuretic hormone).
• Blood tests showing lower than normal sodium concentration
• Difficulty concentrating
• Stroke. Numbness, weakness, or sudden loss of movement in the face, arm, or leg, particularly on one side of the body. This may be accompanied by confusion, visual disturbances, and difficulty speaking.
• Tremor, rigid posture, mask-like face, slow movements, and shuffling gait
• Problems speaking, moving, reacting, or performing activities
• Burning sensation
• Changes in smell
• Tingling, loss of sensation, or color changes in fingers and toes when exposed to cold
• Mouth ulcers in otherwise healthy individuals
• Rapid loss of liver function. Symptoms include fever, chills, fatigue, loss of appetite, stomach pain, feeling unwell, and yellowing of the skin or eyes
• Worsening of psoriasis
• Itchy or painful red scaly skin patches
• Blistering of the skin or mucous membranes

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse.
You can 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 Icomb

Do not store above 30°C. Keep in the original packaging to protect the medicine from moisture.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Do not dispose of any medicine 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 Icomb contains

• The active substances are:

Icomb 5 mg/5 mg hard capsules:
One capsule contains 5 mg of ramipril and 5 mg of amlodipine (as amlodipine besilate).
Icomb 5 mg/10 mg hard capsules:
One capsule contains 5 mg of ramipril and 10 mg of amlodipine (as amlodipine besilate).
Icomb 10 mg/5 mg hard capsules:
One capsule contains 10 mg of ramipril and 5 mg of amlodipine (as amlodipine besilate).
Icomb 10 mg/10 mg hard capsules:
One capsule contains 10 mg of ramipril and 10 mg of amlodipine (as amlodipine besilate).

• Other components are:
  crospovidone, hypromellose, microcrystalline cellulose, glycerol dibehenate, titanium dioxide (E171), gelatin.
  Icomb 5 mg/10 mg, 10 mg/5 mg: iron oxide red (E172)
  Icomb 5 mg/5 mg, 10 mg/5 mg: Brilliant Blue FCF-FD&C Blue No. 1 (E133)
  Icomb 5 mg/5 mg, 10 mg/5 mg: Allura Red AC-FD&C Red No. 40 (E129)
  Icomb 5 mg/10 mg, 10 mg/10 mg: Azorubine, Carmoisine (E122)
  Icomb 5 mg/10 mg, 10 mg/10 mg: Indigotin - FD&C Blue No. 2 (E132)

Description of the appearance of Icomb and pack contents
Icomb 5 mg/5 mg hard capsules:
Hard gelatin capsules with an opaque amethyst (dark pink) body and an opaque amethyst (dark pink) cap, filled with white or almost white granular powder.
Icomb 5 mg/10 mg hard capsules:
Hard gelatin capsules with an opaque flesh-coloured (light pink) body and an opaque brownish-red cap, filled with white or almost white granular powder.
Icomb 10 mg/5 mg hard capsules:
Hard gelatin capsules with an opaque flesh-coloured (light pink) body and an opaque amethyst (dark pink) cap, filled with white or almost white granular powder.
Icomb 10 mg/10 mg hard capsules:
Hard gelatin capsules with an opaque brownish-red body and an opaque brownish-red cap, filled with white or almost white granular powder.
Blister packs containing 10 or 30 hard capsules, packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorization Holder
POLIFARMA S.p.A.
Viale dell’Arte, 69
00144 - Roma, Italy

Manufacturer
Egis Pharmaceuticals PLC
H-1165 Budapest
Bökényföldi út 118-120.
Hungary