Delaman

PACKAGE LEAFLET: INFORMATION FOR THE USER

DELAMAN 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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

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

1. WHAT DELAMAN IS AND WHAT IT IS USED FOR

What DELAMAN is
DELAMAN 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 blood vessels to narrow, 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 the entry of calcium into the smooth muscle cells of blood vessels, causing vasodilation and consequently lowering blood pressure.
The two active substances in DELAMAN work together to lower blood pressure more effectively than when either of them is used alone.

What DELAMAN is used for
For the treatment of high blood pressure (hypertension) in patients in whom blood pressure is not adequately controlled by delapril or manidipine (the two active substances) used alone.
If you do not feel better or feel worse, talk to your doctor.

2. WHAT YOU SHOULD KNOW BEFORE TAKING DELAMAN

Do not take DELAMAN:

• if you are allergic to delapril or other ACE inhibitors, manidipine or other calcium antagonists, or to any of the other ingredients of this medicine (listed in section 6)
• 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 suffer from severe liver impairment
• if you have serious kidney problems (e.g. severe renal failure, if you are on dialysis (a treatment using 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), heart failure)
• if you have problems with 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 DELAMAN 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 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

DELAMAN must not be administered to children and adolescents under 18 years of age.
Warnings and precautions
Talk to your doctor or pharmacist before taking DELAMAN if:

• you have kidney problems
• you have liver problems
• you have certain heart conditions (e.g. coronary artery disease)
• you have disorders due to damage to cerebral blood vessels (cerebrovascular problems)
• you are undergoing LDL apheresis (removal of cholesterol from the blood using a device)
• you plan to undergo 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
• you have a condition associated with persistently high potassium levels in the blood
• you experience swelling of the face, eyes, lips, tongue, throat, or breathing difficulties (see section 4, “rare adverse effects”)
• you have abnormal changes in blood components
• you are scheduled for surgery or need anaesthetics
• you have a rapid heartbeat, dizziness, or a general feeling of weakness, which may indicate low blood pressure
• you must inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). DELAMAN 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 baby if taken during this period (see section "Pregnancy")
• you are taking any of the following medicines for 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 subcutaneous swelling, e.g. in the throat) is increased:
• 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 blood electrolyte levels (e.g. potassium) at regular intervals.

See also the section “Do not take DELAMAN”.
Children and adolescents
DELAMAN must not be administered to children and adolescents under 18 years of age.
Other medicines and DELAMAN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
Your doctor may need to adjust your dose and/or take other precautions if you are taking any of the following medicines:

• 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 DELAMAN
• heparin (used to prevent blood clotting)
• medicines containing lithium (usually used in the treatment of manic-depressive disorders). These medicines should be taken with DELAMAN 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. Special precautions (e.g. blood tests) are recommended in such cases
• 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, medicines used to treat tumours
• medicines for diabetes (both oral and insulin)
• vildagliptin, a medicine used to treat diabetes (see also section: “Do not take DELAMAN”)
• antacids
• medicines that affect the metabolism of one of the active ingredients in DELAMAN, 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 disorders (such as amiodarone, quinidine)
• an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also section: “Do not take DELAMAN” and “Warnings and Precautions”)
• medicines used to treat chronic heart failure in adults (e.g. sacubitril/valsartan) (see also section: “Do not take DELAMAN”)
• racecadotril, a medicine used to treat diarrhoea (see also section: “Do not take DELAMAN”)

Inform your doctor also if you are 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 potassium levels in the blood (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).

DELAMAN with food and drink
DELAMAN should be taken after breakfast.
Do not take the medicine with grapefruit juice, as this may cause excessive lowering of blood pressure.
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 DELAMAN 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 or pharmacist before taking this medicine.
Pregnancy
Your doctor will usually advise you to stop taking DELAMAN before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine instead of DELAMAN.
DELAMAN 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 baby if taken after the third month of pregnancy.
Breastfeeding
DELAMAN 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 DELAMAN will affect your ability to drive or operate machinery.
However, dizziness may occasionally occur during treatment for high blood pressure. If this happens, consult your doctor before engaging in such activities.
DELAMAN contains lactose and a colouring agent
If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
DELAMAN The colouring agent E110 may cause allergic reactions.

3. HOW TO TAKE DELAMAN

Take this medicine exactly as prescribed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
The recommended dose of DELAMAN 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
DELAMAN should be taken in the morning, after the first meal of the day.
Swallow the tablet whole with a sufficient amount of water.
Try to take your daily dose at the same time each day.
The tablet may be divided into equal parts.
Duration of treatment
It is important to continue taking DELAMAN unless otherwise instructed by your doctor.
Take exactly the prescribed dose and do not change it without first consulting your doctor.
C
To prevent misuse by children, the bottle is equipped with a child-resistant cap.
To open and close the bottle, follow the instructions below:

• To open: A) press and turn simultaneously
• To close: B) press and screw simultaneously

Use in children and adolescents
Do not administer DELAMAN to children and adolescents under 18 years of age (see
section 2, “Do not take DELAMAN”).
If you take more DELAMAN 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 DELAMAN
If you accidentally forget to take a dose, continue your treatment as usual.
Do not take a double dose to make up for the missed tablet.
If you stop taking DELAMAN
It is important to continue taking DELAMAN unless otherwise instructed by your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, DELAMAN may cause adverse reactions, although not everyone experiences them.
If adverse reactions should occur, they are usually mild and temporary. However, some of them could be serious and require medical attention.
The frequency 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 in the upright position), hot flushes,
bronchitis, nausea, abdominal pain, digestive disturbances, 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 the number of white blood cells increasing the likelihood of infections, reduction in the
number of platelets with increased risk of bleeding and bruising, anaemia, reduced haemoglobin levels
and haematocrit, loss of appetite, confusion, drowsiness, mood changes, nervousness, anxiety,
abnormal sensations, altered taste, blurred vision, rapid heartbeat, fainting, shortness of breath,
inflammation of the paranasal 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 the 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
inadequate 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 breakdown
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 DELAMAN and seek immediate
medical attention.
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 inadequate 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 blockage,
inflammation of the tongue, development of blisters on the skin, mouth, eyes and genitals with fever
(Stevens-Johnson syndrome), hair loss, psoriasis.
Not known:

• Elevated levels of potassium in the blood (hyperkalaemia)
• Swelling of the face, lips, tongue and/or throat with difficulty in 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)

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 the website
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 DELAMAN

• 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 following the word EXP. The expiry date refers to the last day of that month.
• DELAMAN must be used within two months after first opening the bottle (pack sizes of 14 and 28 tablets).
• DELAMAN must be used within three and a half months after first opening the bottle (pack sizes of 50 and 100 tablets).
• Keep the bottle tightly closed.
• ( For the 100-tablet pack only ) Use all the medicine contained in the first bottle before opening the next one.

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

6. PACKAGING CONTENTS AND OTHER INFORMATION

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

Description of the appearance of DELAMAN and packaging contents
DELAMAN is supplied in amber yellow glass bottles with child-resistant closure, including a desiccant.
Each DELAMAN pack contains 14, 28, 50, or 100 (50x2) pinkish-salmon colored, round, scored tablets.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Promedica S.r.l., Via Palermo 26/A, 43122 Parma, Italy
Manufacturer
Chiesi Farmaceutici S.p.A., Via Palermo 26/A, 43122 Parma, Italy

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Delapril and Manidipine under license from Takeda Pharmaceutical Company, Ltd - Japan