ICOMB 5 mg/5 mg Hard Capsules

Зміст інструкції

1. 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
   1. What Icomb is and what it is used for
   2. Cosa deve sapere prima di prendere Icomb
2. Icomb 5 mg/5 mg capsules and 10 mg/5 mg capsules contains allura red AC-FD&C Red 40 (E129) and
   1. How to take Icomb
   2. Possible side effects
   3. How to store Icomb
   4. Package Contents and Other Information

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

Read this leaflet carefully before you start 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

• 1. What Icomb hard capsules are and what they are used for
• 2. What you need to know before you take 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 ingredients called 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 channel blockers.
Ramipril works as follows:

• decreases the production by the body 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 as follows:

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

2. Cosa deve sapere prima di prendere Icomb

Do not take Icomb

• If you are allergic to ramipril or amlodipine, or to any other calcium channel blocker or ACE inhibitor medicine or to any of the other components of this medicine (listed in section 6). Signs of an allergic reaction can include skin rash, difficulty swallowing or breathing and swelling of the lips, face, throat or tongue.
• If you have a severe narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to provide enough blood to the body).
• If you have had a severe allergic reaction called “angioedema”. Symptoms include itching, hives, red marks on the 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 where the blood flow to the kidneys is reduced (renal artery stenosis).
• During the last 6 months of pregnancy (see section below on “Pregnancy, breastfeeding and fertility”).
• If your blood pressure is low or abnormally unstable. Your doctor will need to make this assessment.
• If you suffer from heart failure after a heart attack.
• If you suffer from diabetes or your kidney function is impaired and you have been treated with a medicine that lowers blood pressure, containing aliskiren.
• If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat a long-term (chronic) type of heart failure in adults, as it increases the risk of angioedema (rapid swelling under the skin in an area such as the throat).

Do not take Icomb if you fall into any of the conditions listed above. If you have any doubts, ask your doctor before
taking Icomb.

Warnings and precautions
Talk to your doctor or pharmacist before taking Icomb.
You must tell 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 disorders to the heart or brain in case of acute low blood pressure.
• if your body has lost a lot of salts or fluids (due to vomiting, diarrhea, sweating more than usual, if you are on a low-salt diet, if you are taking diuretics (water tablets) for a long time or if you are undergoing dialysis).
• if you are going to undergo treatment to reduce an allergy to bee or wasp stings (desensitization).
• if you are going to receive anesthesia. This may be administered for an operation or for a dental procedure. 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 (indicated in blood test results).
• if you are taking medicines or have a condition that may cause a reduction in sodium levels in your blood. Your doctor may require periodic blood tests, especially to check sodium levels in the blood, particularly if you are elderly.
• if you have a collagen-vascular disease such as scleroderma or systemic lupus erythematosus
• if you have a cough. Tell your doctor if you notice a 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 check your kidney function, blood pressure and the amount of electrolytes (e.g. potassium) in your blood at regular intervals. See also what is stated under “Do not take Icomb”.
• if you are taking any of the following medicines, the risk of angioedema may increase: o racecadotril, a medicine used to treat diarrhea. o medicines used to prevent rejection in organ transplantation and for cancer (e.g. temsirolimus, sirolimus, everolimus). o vildagliptin, a medicine used in the treatment of diabetes.
• You must tell your doctor if you think you are (or could become) pregnant. Icomb is not recommended in the first 3 months of pregnancy and can cause serious harm to the baby after the 3rd month of pregnancy (see section “Pregnancy, breastfeeding and fertility”).

If you fall into any of the conditions listed above (or if you have any doubts), ask your doctor before taking
Icomb.
The doctor should monitor the white blood cell count. More frequent monitoring is recommended:

• at the beginning of treatment
• in patients with impaired renal function or collagen vascular diseases or
• when medicines that affect blood cell and blood counts are used.

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

Other medicines and Icomb
See also what is stated under ‘Do not take Icomb’.
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine.
The doctor may need to adjust the dose and/or take other precautions:
If you are taking an angiotensin II receptor blocker (AIIRA) or aliskiren (see also what is stated under ‘Do not take Icomb’ and ‘Warnings and precautions’).
The following medicines can reduce the action 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, norepinephrine or adrenaline, isoprenaline, dobutamine or dopamine. Your doctor will need to check your blood pressure.
• Rifampicin (antibiotic used to treat tuberculosis).
• Hypericum perforatum(St John's Wort - herbal remedy for depression).

Tell your doctor if you are taking any of the following medicines. These can increase the likelihood
of experiencing side effects if you take them at the same time as Icomb:

• Medicines used to relieve pain and inflammation (e.g. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen, indometacin, acetylsalicylic acid).
• Cancer medicines (chemotherapy).
• Medicines to stop organ rejection after a transplant such as cyclosporine.
• Diuretics (water tablets) such as furosemide.
• Medicines that can increase the amount of potassium 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 levels in the blood.)
• Procainamide (for heart rhythm problems).
• Ketoconazole, itraconazole (used to treat fungal infections).
• Erythromycin, clarithromycin (antibiotic agents used to treat certain bacterial infections).
• Ritonavir, indinavir, nelfinavir (called protease inhibitors used to treat patients with HIV).
• Verapamil, diltiazem (for the treatment of certain heart diseases and for high blood pressure).
• Dantrolene (infusion for severe abnormalities of body temperature).
• Sirolimus (to prevent kidney transplant rejection).
• Trimethoprim and cotrimoxazole, also known as trimethoprim/sulfamethoxazole (for infections caused by bacteria).
• Temsirolimus (for cancer).
• Everolimus (to prevent organ transplant rejection).
• Tacrolimus (used to control the immune response to allow the body to accept the transplanted organ).
• Racecadotril (used to treat diarrhea).
• 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 action of the following medicines may be modified by Icomb:

• Medicines for diabetes such as oral medicines to lower blood sugar and insulin. Icomb may lower blood sugar levels. Carefully check your blood sugar levels (glucose) while taking Icomb.
• Lithium (for mental health problems): Icomb may increase the amount of lithium in the blood. The lithium level will need to be closely monitored by your doctor.
• Simvastatin (medicine to reduce cholesterol): Amlodipine increases exposure to simvastatin. If you take Icomb, your doctor may need to reduce the dose of simvastatin.
• Cyclosporine (medicine used to block organ rejection after a transplant).

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

Icomb with food, drinks and alcohol

• Grapefruit juice or grapefruit should not be consumed by people taking Icomb. This is because grapefruit or grapefruit juice can lead to an increase in the levels of the active substance amlodipine in the blood, which can increase the blood pressure lowering effect of Icomb.
• Drinking alcohol during treatment with Icomb may make you feel dizzy or lightheaded. If you are concerned about how much you can drink while taking Icomb, talk to your doctor as medicines used to lower blood pressure and alcohol can intensify their respective sedative effects.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you might be pregnant or are planning a pregnancy, or if you are breastfeeding
with breast milk, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
You should not take Icomb in the first 12 weeks of pregnancy and should not take Icomb after the
13th week as use in pregnancy may be harmful to the baby.
If you become pregnant during treatment with Icomb, tell your doctor immediately.
Switching to a suitable alternative treatment should be initiated before planned pregnancy.

Breastfeeding
You should not take Icomb if you are breastfeeding.
Consult your doctor or pharmacist before taking any medicine.

Fertility
There is insufficient data regarding potential effects on fertility.

Driving and using machines
Icomb may alter your ability to drive vehicles or use machines. If the medicine makes you
feel nauseous, dizzy or tired, or if it gives you a headache, do not drive or use machines and contact your
doctor immediately.

Icomb 5 mg/5 mg capsules and 10 mg/5 mg capsules contains allura red AC-FD&C Red 40 (E129) and

Icomb 5 mg/10 mg capsules and 10 mg/10 mg capsules contains azorubine, carmoisine (E122).
These coloring agents may cause allergic reactions.

3. How to take Icomb

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have
doubts, consult your doctor or pharmacist.
The recommended dose is 1 capsule per day of the concentration established by your doctor.
Depending on the effect, your doctor may modify the dose.
The maximum dose is 1 capsule once a day, of the 10 mg/10 mg concentration.
Take this medicine by mouth at the same time each day, before or after a meal.
Swallow the hard capsule whole with some liquid.
Do not crumble or chew the hard capsule.
Do not take Icomb with grapefruit juice.

Liver and kidney disease
In liver and kidney diseases, the doses may be modified.

Elderly
Your doctor will reduce the initial dose and adjust your treatment more slowly.
In very elderly and debilitated patients, the administration of Icomb capsules should be avoided.

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

If you take more Icomb than you should
Taking too many capsules may cause a lowering of blood pressure or even a
dangerous lowering. It may cause dizziness, lightheadedness, fainting, or a feeling of weakness. If the
drop in blood pressure is sufficient, shock may occur. The skin may become cold
and sweaty and the subject may lose consciousness. Consult a doctor immediately if you take too much
Icomb. Do not drive to the hospital, have someone accompany you or call an ambulance. Bring with you
the packaging of the medicine. This is so that the doctor knows what you have taken.
Excess fluid may accumulate in the lungs (pulmonary edema) causing shortness of
breath that may develop up to 24-48 hours after taking it.

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

If you stop taking Icomb
Your doctor will advise you on the duration of taking the medicine. Your condition may
reappear if you stop taking the medicine before it is recommended.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
manifest.

Stop taking Icomb and contact your doctor immediately if you notice any of the following serious side effects – you may need urgent medical attention:

• Chest pain or tightness that may feel like it is spreading from your chest to your arms and may be accompanied by dizziness and shortness of breath. These may be signs of a heart attack, which is uncommon (may affect up to 1 in 100 people).
• Sudden, severe stomach pain, which may be accompanied by feeling unwell. These may be signs of pancreatitis, which is uncommon (may affect up to 1 in 100 people).
• Swelling of the face, lips or throat that may make it difficult to swallow or breathe and may also be accompanied by an itchy rash. These may be signs of angioedema, which is uncommon (may affect up to 1 in 100 people).
• Severe skin reactions, including skin rashes, mouth sores, blistering or peeling skin (such as Stevens-Johnson syndrome or erythema multiforme), which is very rare (may affect up to 1 in 10,000 people). The reported frequency for toxic epidermal necrolysis is not known.

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 a higher amount of potassium than normal in the blood
• Headache
• Feeling dizzy
• Feeling sleepy
• Fainting
• Irregular or fast heartbeat
• Abnormally low blood pressure
• Abnormally low blood pressure when standing up or sitting up quickly
• Flushing, redness
• Vision disturbances (including double vision)
• Dry, tickly cough
• Inflammation and irritation of the major airways of the lungs
• Inflammation of the sinuses (nasal cavities)
• Difficulty breathing
• Inflammation or irritation of the stomach or intestines
• Digestive disorders
• Abdominal discomfort
• Indigestion
• Diarrhoea
• Feeling sick to the stomach
• Vomiting
• Stomach pain
• Changes in bowel habits
• Constipation
• Skin rash
• Muscle cramps
• Muscle pain
• Chest pain
• Feeling tired
• Swelling of the limbs, including swelling of the ankles

Uncommon: may affect up to 1 in 100 people

• Increase in the number of certain white blood cells shown by blood tests
• Loss or decrease of appetite (anorexia)
• Feeling depressed
• Changes in mood, including anxiety
• Feeling more nervous than usual
• Feeling restless
• Difficulty sleeping
• Dizziness
• Sensation of tingling, prickling or burning
• Loss or alteration of taste
• Reduced sensitivity
• Tremor or agitation
• Vision disturbances (including blurred vision)
• Ringing in the ears
• Increased heartbeat
• Irregular heartbeat
• Sneezing/itchy nose/runny nose
• Cough
• Difficulty breathing or worsening of asthma
• Blood tests showing changes in pancreas function
• A swelling in the intestine called "intestinal angioedema" which presents with symptoms such as abdominal pain, nausea, vomiting and diarrhoea
• Inflammation of the stomach
• Dry mouth
• Blood tests showing changes in liver function
• Red or purple spots or blemishes 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 with urination
• Increased need to urinate, especially at night
• Increased urine volume or needing to urinate more frequently than usual during the day
• Blood or urine tests showing worsening kidney function
• Inability to get or maintain an erection
• Decreased sexual drive in men or women
• Breast enlargement in men
• Fever
• Feeling weak or lacking energy
• Pain
• Feeling unwell
• Weight gain or loss
• Swelling of the hands or legs/feet

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

• Blood tests showing a decrease in the number of red blood cells, white blood cells, platelets or in the amount of hemoglobin
• Feeling confused
• Problems with balance
• Red, itchy and/or swollen eyes
• Hearing problems
• Narrowing of blood vessels
• Decreased blood flow
• Inflammation of blood vessels
• Red and swollen tongue
• Yellowing of the skin
• Liver damage/inflammation
• Scaling, delamination and exfoliation of the skin, which may be accompanied by itching, redness and hair loss
• Hives
• Nail problem (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 and itchy rash, watery and itchy eyes, feeling of tightness in the chest and shortness of breath
• Excess sugar in the blood
• Muscle stiffness, tremors and/or movement disorders
• Feeling of weakness, numbness and pain, usually in hands and feet
• Enlargement of the gum tissue
• Increased sensitivity to sunlight

Not known: frequency cannot be estimated from the available data

• Blood tests showing that the immune system may be overactive
• The bone marrow does not produce enough blood cells or platelets
• Blood tests showing an insufficient amount of cells present in the blood
• The body retains too much water. You may have concentrated urine (dark-colored urine), feel unwell or sick, have muscle cramps, confusion and seizures that may be due to inappropriate secretion of ADH (anti-diuretic hormone).
• Blood tests showing a lower than normal concentration of sodium
• Difficulty concentrating
• Stroke. Sudden numbness, weakness or loss of movement of the face, arm or leg, especially 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 a shuffling, unsteady walk
• Problems with speaking, moving, reacting or performing activities
• Burning sensation
• Alteration of smell
• Tingling, loss of sensation or change in color of the fingers of hands and feet when cold
• Mouth ulcers in otherwise healthy people
• Rapid deterioration of liver function. Symptoms include fever, chills, fatigue, loss of appetite, stomach pain, feeling unwell and yellowing of 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 get any side effects, even those not listed in this leaflet, please tell your
doctor, pharmacist or nurse. You can also report side effects directly through 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 at temperatures above 30°C. Store in the original packaging to protect the
medicinal product from humidity.
Keep this medicine out of the sight and reach of children.
Do not use this medicine beyond the expiry date that is reported on the packaging after “Exp.”. The expiry
date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines that you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Icomb Contains

• The active ingredients are:

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

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

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

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

• The other ingredients are: crospovidone hypromellose microcrystalline cellulose glycerol dibehenate titanium dioxide (E171) gelatin Icomb 5 mg/10 mg, 10 mg/5 mg: red iron oxide (E172) Icomb 5 mg/5 mg, 10 mg/5 mg: brilliant blue FCF-FD&C Blue 1 (E133) Icomb 5 mg/5 mg, 10 mg/5 mg: allura red AC-FD&C Red 40 (E129) Icomb 5 mg/10 mg, 10 mg/10 mg: azorubine, carmoisine (E122) Icomb 5 mg/10 mg, 10 mg/10 mg: indigotine -FD&C Blue2 (E132)

Description of the appearance of Icomb and package contents

Icomb 5 mg/5 mg hard capsules:
Hard gelatin capsules with an opaque amethyst (dark pink) body, and with an opaque amethyst (dark pink) cap, filled with a white or almost white granular powder.

Icomb 5 mg/10 mg hard capsules:
Hard gelatin capsules with an opaque flesh-colored (light pink) body, and with an opaque brownish-red cap, filled with a white or almost white granular powder.

Icomb 10 mg/5 mg hard capsules:
Hard gelatin capsules with an opaque flesh-colored (light pink) body, and with an opaque amethyst (dark pink) cap, filled with a white or almost white granular powder.

Icomb 10 mg/10 mg hard capsules:
Hard gelatin capsules with an opaque brownish-red body, and with an opaque brownish-red cap, filled with a white or almost white granular powder.
10 and 30 hard capsules in blisters, in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
POLIFARMA S.p.A.
Viale dell’Arte, 69

• 00144 - Rome

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