FRAGOR 30 mg/10 mg Coated Tablet

Зміст інструкції

1. FRAGOR 30 mg / 10 mg tablets
   1. WHAT FRAGOR IS AND WHAT IT IS USED FOR
   2. WHAT YOU NEED TO KNOW BEFORE TAKING FRAGOR
   3. HOW TO TAKE FRAGOR
   4. POSSIBLE SIDE EFFECTS
   5. HOW TO STORE FRAGOR
   6. CONTENTS OF THE PACK AND OTHER INFORMATION

FRAGOR 30 mg / 10 mg tablets

(Delapril hydrochloride + manidipine hydrochloride)

Read this leaflet carefully before taking this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor. See section 4.

1. WHAT FRAGOR IS AND WHAT IT IS USED FOR

What Fragor is
Fragor is a combination of two active ingredients: delapril hydrochloride and manidipine hydrochloride.
Delapril hydrochloride belongs to a group of drugs known as angiotensin converting enzyme (ACE) inhibitors. Angiotensin II is a substance produced
in the body that causes constriction of blood vessels, thus causing an increase in
blood pressure. Delapril hydrochloride prevents the production of angiotensin II, thereby causing a reduction in pressure.
Manidipine hydrochloride belongs to a group of drugs called Calcium antagonists, which
prevent the entry of calcium into the smooth muscle cells present in blood vessels, thereby causing
vasodilation with a consequent reduction in blood pressure.
The two active ingredients present in FRAGOR contribute to lowering blood pressure more
effectively than their use alone.

What Fragor is used for
For the treatment of high blood pressure (hypertension) in patients in whom it is not
adequately controlled by the use of delapril or manidipine (the two active ingredients) alone.

CONTENTS OF THIS LEAFLET:

• 1. What Fragor is and what it is used for
• 2. What you need to know before you take Fragor
• 3. How to take Fragor
• 4. Possible side effects
• 5. How to store Fragor
• 6. Contents of the pack and other information

2. WHAT YOU NEED TO KNOW BEFORE TAKING FRAGOR

Do not take Fragor:

• if you are allergic to delapril or other ACE inhibitors, manidipine or other Calcium-antagonists, or to any of the other ingredients of FRAGOR
• if you have suffered from allergic reactions, such as swelling of the face, eyes, lips, tongue, or throat, or difficulty breathing with previous treatments of ACE inhibitors or if you or a member of your family has had these symptoms in other circumstances
• if you suffer from severe liver failure
• if you suffer from severe kidney problems (for example, severe renal insufficiency, if you are on dialysis (an artificial kidney treatment), if you have had a kidney transplant or if you suffer from renal artery stenosis (narrowing of the renal artery) if you have only one kidney)
• if you suffer from heart problems (for example, if you have recently had a heart attack or angina pectoris (chest pain due to inadequate oxygen supply to the heart), heart failure)
• if you have problems with aortic stenosis (narrowing of the main blood vessel exiting the heart) or if you have hypertrophic cardiomyopathy (heart muscle disease)
• if you have hyperactivity of the adrenal glands that may lead to a decrease in potassium levels in the blood
• if you are pregnant for more than three months. (it is best to avoid Fragor even in the early stages of pregnancy - see the section “Pregnancy”).
• if you suffer from diabetes or your kidney function is impaired and you are being treated with a medicine that lowers blood pressure, containing aliskiren.
• If you have taken or are taking sacubitril/valsartan, a medicine used to treat a type of long-term (chronic) heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin in areas such as the throat). If you are taking any of the following medicines, the risk of angioedema may be increased.
• Racecadotril, a medicine used to treat diarrhea.
• Medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus).
• Vildagliptin, a medicine used to treat diabetes.

Fragor should not be administered to children and adolescents under the age of 18 years.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Fragor.

Take special care with Fragor, especially:

• if you suffer from kidney problems
• if you suffer from liver problems
• if you suffer from certain heart problems (for example, coronary artery disease)
• if you suffer from disorders due to damage to the blood vessels in the brain (cerebrovascular problems)
• if you are undergoing LDL apheresis (removal of cholesterol from the blood with a machine)
• if you intend to undergo desensitization treatment to reduce the effects of allergy to bee or wasp stings
• if you suffer from a collagen-vascular disease such as systemic lupus erythematosus or scleroderma
• if you have diabetes.

Also, tell your doctor before taking Fragor:

• if you have a condition associated with a persistently high level of potassium in the blood
• if you experience swelling of the face, eyes, lips, tongue, or throat, or difficulty breathing (see section 4, “rare side effects”)
• if you experience abnormal changes in blood components
• if you are to undergo surgery or receive anesthetics
• if you have a rapid heartbeat, dizziness, or a feeling of general weakness that may indicate low blood pressure
• if you are undergoing peritoneal dialysis
• you must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Fragor is not recommended in early pregnancy, and should not be taken if you are pregnant for more than three months, as it can cause serious harm to the baby if taken during this period (see the section Pregnancy)
• if you are taking any of the following medicines used to treat high blood pressure:
• an "angiotensin II receptor blocker" (AIIRA) (also known as sartans - for example valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes
• aliskiren
• if you are taking any of the following drugs, the risk of angioedema (rapid swelling under the skin in areas such as the throat) is greater:
• sirolimus, everolimus and other drugs belonging to the class of mTOR inhibitors (used to prevent rejection of transplanted organs).

The 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 Fragor”.

Children and adolescents
Fragor should not be administered to children and adolescents under the age of 18 years

Other medicines and Fragor
Tell your doctor if you are taking, have recently taken or might take any other
medicines, including those available without a prescription.
In particular, it is important that you tell your doctor if you are taking any of the
following medicines. The doctor may need to adjust the dose and/or take other
precautions:

• diuretics (used to eliminate water from the body by increasing urine production) and other medicines that lower your blood pressure. These medicines can intensify the blood pressure lowering effect of Fragor
• heparin (used to prevent blood clotting)
• medicines containing lithium (usually used in the treatment of manic-depressive disorders). These medicines must be taken with Fragor only under strict medical supervision
• some pain relievers (for example, non-steroidal anti-inflammatory drugs such as aspirin)
• antidepressants, antipsychotics (used in the treatment of schizophrenia and other mental disorders) and anesthetics
• medicines that stimulate the sympathetic nervous system (e.g. cold medicines)
• salts containing potassium or potassium-sparing diuretics. In this case, special precautions are recommended (e.g. blood tests)
• digoxin (used to treat heart disorders)
• medicines that modify blood components (for example, allopurinol, used to treat gout), procainamide (for the treatment of irregular heartbeat), corticosteroids, immunosuppressants used to treat autoimmune diseases or following transplants to prevent rejection, drugs used to treat cancer)
• medicines for diabetes (both oral and insulin)
• antacids
• medicines that affect the metabolism of one of the active ingredients contained in Fragor, such as cimetidine (used to treat stomach ulcers) or some antibiotics or antifungals (used to treat fungal infections), phenytoin, carbamazepine, phenobarbital, rifampicin, terfenadine and astemizole, Class III antiarrhythmics used for heart rhythm problems (such as amiodarone, quinidine).
• an angiotensin II receptor blocker (AIIRA) or aliskiren (see also what is stated under “Do not take Fragor” and “Warnings and precautions”).

This indication applies especially if you are also taking:

• Drugs usually used to prevent rejection of transplanted organs (sirolimus, everolimus and other drugs belonging to the class of mTOR inhibitors). See section “Warnings and precautions”.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics and other medicines that can increase the amount of potassium in the blood (such as trimethoprim and cotrimoxazole for treating bacterial infections; cyclosporine, an immunosuppressant used to prevent rejection of organs; and heparin, a medicine used to thin the blood and prevent the formation of clots).

Fragor with food and drink
Fragor should be taken after breakfast.
Do not take the medicine with grapefruit juice, as blood pressure may
drop too much.
Drinking alcohol may cause a sudden drop in your blood pressure
when standing up.
Avoid foods high in salt (containing a high amount of sodium chloride) as they may reduce
the effectiveness of Fragor in lowering blood pressure.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, ask your doctor for advice before taking this medicine.

Pregnancy
As a rule, your doctor will advise you to stop taking Fragor before starting
pregnancy or as soon as you find out you are pregnant and will advise you to
take another medicine instead of Fragor.
Fragor is not recommended in early pregnancy, and should not be taken if you are pregnant for more than three months, as it can cause serious harm to the baby if taken after
the third month of pregnancy.

Breastfeeding
Fragor is not recommended for mothers who are breastfeeding and the doctor may choose another
treatment if you wish to breastfeed, especially if your baby is newly born or was
born prematurely.

Driving and operating machinery
It is unlikely that Fragor will affect your ability to drive vehicles or operate machinery.
However, dizziness can occasionally occur during treatment for high blood pressure. If this
happens to you, consult your doctor before engaging in these activities.

Fragor contains lactose and coloring agent
If your doctor has diagnosed you with intolerance to some sugars, contact him before taking
this medicine.
The coloring agent E110 may cause allergic reactions.

3. HOW TO TAKE FRAGOR

Take this medicine following exactly the instructions of your doctor. If you have any doubts
consult your doctor.
The recommended dose of Fragor is one tablet, once a day.

Dose reduction
If you are over 65 years of age, or if you suffer from kidney or liver disorders, your doctor
may prescribe you a suitably reduced dose.

Method of administration
Fragor should be taken in the morning, after breakfast.
Swallow the tablet whole, with a sufficient amount of water.
You should try to take your daily dose every day at the same time.

Duration of treatment
It is important to continue taking Fragor unless otherwise indicated by your doctor.
Take exactly the prescribed dose and do not modify it without first consulting your doctor.

Use in children and adolescents
Do not administer Fragor to children and adolescents under 18 years of age (see paragraph
2, “Do not take Fragor”).

If you take more Fragor than you should
If you accidentally take too many tablets, contact your doctor immediately
as this may excessively reduce your blood pressure.

If you forget to take Fragor
If you accidentally forget to take a dose of the medicine, continue normally with the
therapy. Do not take a double dose to compensate for the forgotten single tablet.

If you stop taking Fragor
It is important to continue taking Fragor unless otherwise indicated by your doctor.
If you have any doubts about the use of this medicine, consult your doctor.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Fragor can cause side effects, although not everybody gets them.
If you get any side effects, they are usually mild and temporary.
However, some of these could be serious and require medical attention. The frequency
with which side effects occur is classified into the following categories:

Common side effects:
Very common side effects:
Cough, fluid retention in the tissues with swelling, headache.

Other common side effects:
Decreased number of white blood cells, apathy, loss of balance, impaired balance,
feeling of dizziness, fast heartbeat, very low blood pressure (especially when
standing up), flushing, bronchitis, nausea, abdominal pain, digestive disorders,
fatigue, altered blood tests (e.g. changes indicating impaired liver function,
increased potassium levels).

Uncommon side effects:
Anemia due to deficiency or insufficient number of new blood cells produced by the bone
marrow, severe decrease in the number of white blood cells making infections more likely, decreased
number of platelets with increased risk of bleeding and bruising,
anemia, decreased amount of hemoglobin and red blood cell volume ratio, loss of
appetite, confusion, drowsiness, mood changes, nervousness, anxiety, altered sensations,
altered sense of taste, blurred vision, fast heartbeat, fainting,
shortness of breath, inflammation of the sinuses and nasal mucosa (runny nose), sore throat,
vomiting, diarrhea, constipation, dry mouth, gallstones (especially in case of
pre-existing gallbladder infection), erythema, itching, skin inflammation with redness and
itching (eczema), excessive sweating, stiffness of muscles and joints, pain in legs
and arms, impaired kidney function, excess protein in the urine,
difficulty getting or maintaining an erection (impotence), weakness, feeling unwell, altered
blood tests (e.g. changes indicating impaired kidney function).

Rare side effects:
Allergic reactions, decreased libido, drowsiness, heart attack, irregular heartbeat,
chest pain due to insufficient oxygen supply to the heart (angina pectoris), chest pain,
stroke, stomach pain, hives, abnormal skin redness,
muscle cramps, acute kidney failure, presence of urea (a waste product
normally excreted in urine) in the blood, irritability, altered blood tests (e.g. increased
bilirubin, changes indicating impaired function for example cardiac or
muscular).
Rare side effects caused by this type of medicine can include: swelling of the
face, eyes, lips, tongue, or throat, or difficulty breathing.
If you notice any of these reactions during treatment, stop taking Fragor and
seek immediate medical help.
Very rare side effects (including isolated reports):
Anemia due to excessive destruction of red blood cells, in patients with pre-existing angina pectoris
(chest pain due to insufficient oxygen supply to the heart) increased frequency,
duration and intensity of angina attacks and heart attack, poor blood circulation causing numbness and pallor of the toes and hands (Raynaud's phenomenon), difficulty breathing, inflammation of the pancreas, intestinal blockage, inflammation of the
tongue, appearance of blisters on the skin, mouth, eyes and genitals with fever (Stevens-Johnson
syndrome), hair loss, psoriasis.

Side effects with unknown frequency(the frequency cannot be estimated from the available
data)

• High levels of potassium in the blood (hyperkalemia)
• Swelling of the face, lips, tongue and/or throat with difficulty swallowing or breathing (angioedema)
• Kidney problems: significantly reduced urine production (acute kidney injury)
• Muscle pain
• Breast enlargement with or without breast tenderness in men (gynecomastia)
• Cloudy fluid (when dialysis is performed through a catheter in the abdomen)

If any of these side effects get serious, or if you notice any side effects not listed in this leaflet

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed
in this leaflet.
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 FRAGOR

Keep this medicine out of the sight and reach of children.

• Do not use this medicine after the expiry date which is stated on the package and label after “Scad.”. 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 you no longer use. This will help protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Fragor contains
The active ingredients are delapril hydrochloride and manidipine hydrochloride.
Each Fragor 30 mg/10 mg tablet contains 30 mg of delapril hydrochloride and 10
mg of manidipine hydrochloride, respectively.
The excipients are: lactose monohydrate, low substituted hydroxypropylcellulose,
hydroxypropylcellulose, magnesium stearate, riboflavin, E110 aluminium lake.

Description of the appearance of Fragor and contents of the pack
Fragor is supplied in Alu-Alu blisters.
Each pack of Fragor contains 28 divisible, round, salmon pink tablets.

Marketing Authorisation Holder and Manufacturers

Marketing Authorisation Holder
Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43122 Parma, Italy

Manufacturers
Chiesi Farmaceutici S.p.A, Via San Leonardo 96, 43122 Parma, Italy
Fine Foods & Pharmaceuticals N.T.M. S.p.A.Via Grignano, 43 24041 Brembate (BG), Italy