Fragor

PACKAGE LEAFLET: INFORMATION FOR THE USER

FRAGOR 30 mg / 10 mg tablets

(Delapril hydrochloride + manidipine hydrochloride)
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.
• 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. See section 4.

CONTENTS OF THIS LEAFLET:

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

1. WHAT FRAGOR IS AND WHAT IT IS USED FOR

What Fragor is
Fragor is a combination of two active substances: delapril hydrochloride and manidipine hydrochloride.
Delapril hydrochloride belongs to a group of medicines known as angiotensin-converting enzyme inhibitors (ACE inhibitors). Angiotensin II is a substance produced in the body that causes narrowing of the blood vessels, thereby increasing blood pressure. Delapril hydrochloride prevents the formation of angiotensin II, thus reducing blood pressure.
Manidipine hydrochloride belongs to a group of medicines called calcium antagonists, which block calcium from entering the smooth muscle cells of blood vessels, resulting in vasodilation and a consequent reduction in blood pressure.
The two active substances in FRAGOR work together to lower blood pressure more effectively than when either is used alone.

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

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 experienced allergic reactions such as swelling of the face, eyes, lips, tongue, throat, or difficulty breathing during previous treatments with ACE inhibitors, or if you or a family member has had these symptoms under other circumstances
• if you have severe liver impairment
• if you have severe kidney problems (e.g. severe renal failure, if you are on dialysis (a treatment involving an artificial kidney), if you have had a kidney transplant, or if you have renal artery stenosis (narrowing of the renal artery) and have only one kidney
• if you have heart problems (e.g. if you recently had a heart attack or angina pectoris (chest pain due to inadequate oxygen supply to the heart), or heart failure)
• if you have aortic stenosis (narrowing of the main blood vessel leaving the heart) or hypertrophic cardiomyopathy (a disease of the heart muscle)
• if you have overactivity of the adrenal glands which may lead to low potassium levels in the blood
• if you are more than three months pregnant. (It is also advisable to avoid Fragor during early pregnancy – see section “Pregnancy”).
• 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 a type of long-term (chronic) heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin, e.g. in the throat). If you are taking any of the following medicines, the risk of angioedema may be increased:
  • Racecadotril, a medicine used to treat diarrhoea.
  • 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 must not be administered to children and adolescents under 18 years of age.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Fragor.
Be especially cautious with Fragor if:

• you have kidney problems
• you have liver problems
• you have certain heart conditions (e.g. coronary artery disease)
• you have conditions due to damage of cerebral blood vessels (cerebrovascular disorders)
• you are undergoing LDL apheresis (removal of cholesterol from the blood using a machine)
• you are planning desensitization treatment to reduce the effects of allergy to bee or wasp stings
• you have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma
• you have diabetes.

Additionally, inform your doctor before taking Fragor:

• if you have a condition associated with persistently high potassium levels in the blood
• if you experience swelling of the face, eyes, lips, tongue, throat, or difficulty breathing (see section 4, “Rare adverse effects”)
• if you have abnormal changes in blood components
• if you are scheduled for surgery or will be receiving anaesthetics
• if you have a rapid heartbeat, dizziness, or a general feeling of weakness, which may indicate low blood pressure
• if you are undergoing peritoneal dialysis
• you must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Fragor is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause severe harm to the unborn child if taken during this period (see section “Pregnancy”)
• 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 – e.g. valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes
  • aliskiren
• if you are taking any of the following medicines, the risk of angioedema (rapid swelling under the skin, e.g. in the throat) is greater:
  • sirolimus, everolimus, and other medicines belonging to the class of mTOR inhibitors (used to prevent rejection of transplanted organs).

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 Fragor”.
Children and adolescents
Fragor must not be administered to children and adolescents under 18 years of age.
Other medicines and Fragor
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
In particular, it is important to inform your doctor if you are taking any of the following medicines. Your doctor may consider it necessary to adjust the dose and/or take additional precautions:

• diuretics (used to eliminate water from the body by increasing urine production) and other medicines that lower your blood pressure. These medicines may enhance 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 should be taken with Fragor only under close medical supervision
• certain painkillers (e.g. non-steroidal anti-inflammatory drugs such as aspirin)
• antidepressants, antipsychotics (used to treat schizophrenia and other mental disorders), and anaesthetics
• medicines that stimulate the sympathetic nervous system (e.g. cold remedies)
• potassium-containing salts or potassium-sparing diuretics. In such cases, special precautions (e.g. blood tests) are recommended
• digoxin (used to treat heart disorders)
• medicines that affect blood components (e.g. allopurinol, used to treat gout), procainamide (for irregular heartbeat), corticosteroids, immunosuppressants used to treat autoimmune diseases or to prevent transplant rejection, and medicines used to treat tumours
• medicines for diabetes (both oral and insulin)
• antacids
• medicines that affect the metabolism of one of the active substances in Fragor, such as cimetidine (used to treat gastric ulcers), certain antibiotics or antifungals (used to treat fungal infections), phenytoin, carbamazepine, phenobarbital, rifampicin, terfenadine, astemizole, class III antiarrhythmics used for heart rhythm problems (such as amiodarone, quinidine)
• an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections “Do not take Fragor” and “Warnings and precautions”).

This warning is particularly relevant if you are also taking:

• Medicines usually used to prevent rejection of transplanted organs (sirolimus, everolimus, and other mTOR inhibitors). See section “Warnings and precautions”.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase blood potassium levels (such as trimethoprim and cotrimoxazole for treating bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent transplant rejection; and heparin, a medicine used to thin the blood and prevent clotting).

Fragor with food and drink
Fragor should be taken after breakfast.
Do not take the medicine with grapefruit juice, as this may cause your blood pressure to drop too much.
Alcohol consumption may cause a sudden drop in blood pressure when standing up.
Avoid foods high in salt (containing high amounts of sodium chloride), as they may reduce the effectiveness of Fragor in lowering blood pressure.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
Pregnancy
Your doctor will usually advise you to stop taking Fragor before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine.
Fragor is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the unborn child if taken beyond the third month of pregnancy.
Breastfeeding
Fragor is not recommended for breastfeeding mothers. Your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is newborn or was born prematurely.
Driving and using machines
It is unlikely that Fragor will affect your ability to drive or use machines.
However, dizziness may occasionally occur during treatment for high blood pressure. If this happens, consult your doctor before engaging in such activities.
Fragor contains lactose and a colouring agent
If your doctor has diagnosed you with an intolerance to certain sugars, consult him/her before taking this medicine.
The colouring agent E110 may cause allergic reactions.

3. HOW TO TAKE FRAGOR

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.
The recommended dose of Fragor is one tablet once daily.
Dose reduction
If you are over 65 years of age, or if you have renal or hepatic impairment, your doctor may prescribe you an appropriately reduced dose.
Method of administration
Fragor should be taken in the morning, after the first meal.
Swallow the tablet whole with a sufficient amount of water.
Try to take your daily dose at the same time each day.
Duration of treatment
It is important to continue taking Fragor unless otherwise instructed by your doctor.
Take exactly the prescribed dose and do not change 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 section 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 could excessively lower your blood pressure.
If you forget to take Fragor
If you accidentally miss a dose, continue your treatment as usual. Do not take a double dose to make up for the missed tablet.
If you stop taking Fragor
It is important to continue taking Fragor unless otherwise instructed by your doctor.
If you have any questions about the use of this medicine, consult your doctor.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Fragor may cause adverse reactions, although not everyone experiences them.
If adverse reactions do occur, they are usually mild and temporary.
However, some of these could be serious and require medical attention. The frequency of occurrence of adverse reactions is classified into the following categories:

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

Other common side effects:
Reduction in the number of white blood cells, apathy, loss of balance, disturbance of equilibrium, dizziness, rapid heartbeat, very low blood pressure (especially when standing), hot flushes, bronchitis, nausea, abdominal pain, digestive disorders, fatigue, abnormal blood tests (e.g. changes indicating impaired liver function, increased potassium levels).

Uncommon side effects:
Anaemia due to deficiency or insufficient production of new blood cells by the bone marrow, severe reduction in white blood cells increasing the likelihood of infections, reduced platelet count with increased risk of bleeding and bruising, anaemia, reduced haemoglobin levels and decreased ratio of red blood cell volume, loss of appetite, confusion, drowsiness, mood changes, nervousness, anxiety, altered sensations, altered sense of taste, blurred vision, rapid heartbeat, fainting, shortness of breath, inflammation of the sinuses and nasal mucosa (runny nose), sore throat, vomiting, diarrhoea, constipation, dry mouth, gallstones (especially in case of pre-existing gallbladder infection), erythema, itching, skin inflammation with redness and itching (eczema), excessive sweating, muscle and joint stiffness, pain in the legs and arms, impaired kidney function, presence of excess protein in urine, difficulty achieving or maintaining erection (impotence), weakness, malaise, abnormal blood tests (e.g. changes indicating impaired kidney function).

Rare side effects:
Allergic reactions, reduced libido, drowsiness, heart attack, irregular heartbeat, chest pain due to insufficient oxygen supply to the heart (angina pectoris), chest pain, stroke, stomach pain, urticaria, abnormal redness of the skin, muscle cramps, acute kidney failure, presence of urea (a waste product normally excreted in urine) in the blood, irritability, abnormal blood tests (e.g. increased bilirubin, changes indicating impaired function, for example cardiac or muscular).

Rare adverse reactions caused by this type of medicine may include: swelling of the face, eyes, lips, tongue, throat or difficulty breathing.
If you experience any of these reactions during treatment, stop taking Fragor immediately and seek medical help right away.

Very rare side effects (including isolated reports):
Anaemia due to excessive breakdown 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 paleness of fingers and toes (Raynaud's phenomenon), breathing difficulties, inflammation of the pancreas, intestinal obstruction, 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 (frequency cannot be determined from the available data):

• Elevated potassium levels in the blood (hyperkalaemia)
• 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 (gynaecomastia)
• Cloudy fluid (when performing dialysis through a catheter in the abdomen)

If any of the side effects worsen, or if you notice any side effect not listed in this leaflet, inform your doctor or pharmacist.

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

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

• Do not use this medicine after the expiry date stated on the carton and label after "Exp.". The expiry date refers to the last day of that month.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

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

Description of the appearance of Fragor and the packaging contents
Fragor is supplied in Alu-Alu blisters.
Each box of Fragor contains 28 pinkish-red, round, scored 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