Diladel

Patient Information Leaflet: Information for the Patient

DILADEL 60 mg modified-release tablets

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

Contents of this leaflet:

1. What DILADEL is and what it is used for
2. What you need to know before taking DILADEL
3. How to take DILADEL
4. Possible side effects
5. How to store DILADEL
6. Package contents and other information

1. What DILADEL is and what it is used for

DILADEL contains the active substance diltiazem hydrochloride, which belongs to a group of medicines called calcium channel blockers (calcium antagonists), used for the treatment of high blood pressure.
DILADEL is indicated for the treatment of:

• chest pain (angina pectoris) due to exertion, heart attack, or problems with the arteries supplying blood to the heart (Prinzmetal's angina);
• mild to moderate cases of high blood pressure.

2. What you need to know before taking DILADEL

Do not take DILADEL

• if you are allergic to diltiazem or to any of the other ingredients of this medicine (listed in section 6);
• if you have low blood pressure (systolic pressure below 90 mmHg);
• if you have acute myocardial infarction with lung complications;
• if you have an irregular heartbeat due to certain heart conditions (sino-atrial node syndrome, atrioventricular block, sino-atrial block) and do not have a functioning pacemaker;
• if you have a very slow heartbeat (severe bradycardia, less than 40 beats per minute);
• if you have severe heart problems, possibly with lung complications (left ventricular failure with pulmonary congestion and congestive heart failure);
• if you are using medicines such as dantrolene and amiodarone by infusion (see section “Other medicines and DILADEL”);
• if you are using a medicine containing ivabradine for the treatment of certain heart conditions;
• if you are using a medicine containing lomitapide, used to treat high cholesterol levels (see section “Other medicines and DILADEL”);
• if you are pregnant or suspect you may be, if you are breastfeeding, or if you are a woman of childbearing age not using contraception to prevent pregnancy.

Warnings and precautions
Talk to your doctor or pharmacist before taking DILADEL.
Speak with your doctor if you have a history of heart failure, unusual shortness of breath, slow heartbeat, or low blood pressure. Cases of kidney damage have been reported in patients with these conditions; your doctor may need to monitor your kidney function.
Use this medicine with great caution and inform your doctor in the following cases:

• if you have heart problems such as reduced left ventricular function, slow heartbeat (bradycardia), or other heart disorders (first-degree atrioventricular block);
• if you are elderly or have kidney or liver problems;
• if you are also taking other medicines that lower blood pressure, as your blood pressure could drop excessively (see “Other medicines and DILADEL”);
• if you are at risk of intestinal obstruction, since diltiazem affects intestinal function; if you are undergoing surgery, inform the anaesthetist that you are taking this medicine.

In the cases listed above, you may be prescribed different doses than normally used.
Your doctor will perform periodic checks of your heart, liver, and kidney function (during and especially at the beginning of treatment), and your blood sugar levels if you have diabetes mellitus, as there is a risk of increased blood glucose.
Calcium antagonists, such as diltiazem, may be associated with mood changes, including depression.
The use of DILADEL may cause bronchoconstriction (bronchospasm), including worsening of asthma, particularly in patients who already have breathing difficulties or after dose escalation. During treatment with DILADEL, your doctor will monitor your respiratory function.
Children
This medicine is not recommended for children.
Other medicines and DILADEL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not use this medicine in combination with:

• dantrolene (infusion), a medicine used for muscle spasms and treatment of a type of fever called malignant hyperthermia;
• amiodarone, a medicine used to treat certain heart conditions;
• medicines containing lomitapide, used to treat high cholesterol levels. Diltiazem can increase lomitapide concentration, which may increase the likelihood and severity of liver-related adverse effects.

Use particular caution and inform your doctor if you are taking any of the following medicines (in some cases, your doctor may adjust the dose of diltiazem or of the other medicines):

• antihypertensives, medicines that reduce blood pressure. If you are taking this medicine together with an antihypertensive, your doctor will closely monitor your blood pressure;
• nitrates, medicines that dilate blood vessels. If you are taking this medicine, nitrates will be prescribed at gradually increasing doses;
• theophylline, a medicine used to treat asthma;
• beta-blockers, medicines used for high blood pressure and heart problems. In this case, your doctor will closely monitor heart function, especially at the beginning of treatment. An increased risk of depression has been reported when diltiazem is administered together with beta-blockers (see section 4);
• medicines for heart conditions in general, and particularly cardioactive glycosides (e.g., digoxin). Exercise particular caution, especially if you are elderly or taking high doses of diltiazem;
• medicines used for heart rhythm disorders (antiarrhythmics). In this case, your doctor will closely monitor your heart function;
• carbamazepine and phenytoin, medicines used for epilepsy. In this case, your doctor will monitor blood levels of carbamazepine and phenytoin;
• rifampicin, a medicine for bacterial infections (antibiotic);
• medicines used for stomach ulcers, known as H2-antagonists, such as cimetidine and ranitidine. If treatment with these medicines is started or stopped during DILADEL therapy, your doctor may adjust the dose of diltiazem;
• cyclosporine, a medicine used to prevent organ transplant rejection;
• medicines for depression (antidepressants) such as imipramine and tricyclic antidepressants;
• medicines used for mental disorders (antipsychotics), including lithium;
• medicines used for anaesthesia (see section “Warnings and precautions”);
• contrast media for X-ray examinations, as they may enhance the effects of diltiazem on the heart, such as lowering blood pressure;
• antiplatelet agents, medicines that prevent aggregation of blood cells called platelets, thereby increasing blood fluidity;
• benzodiazepines, medicines for anxiety or depression, such as midazolam and triazolam, since diltiazem increases blood concentrations of these drugs;
• corticosteroids, medicines used to treat inflammation. Your doctor will monitor you and adjust the corticosteroid dose if necessary;
• statins, medicines used to lower blood cholesterol, because there may be a risk of serious muscle damage (myopathy and rhabdomyolysis);
• cilostazol, a medicine used to relieve leg pain during walking. DILADEL increases the activity of cilostazol.

DILADEL and beverages
Avoid taking this medicine with grapefruit juice, as it may increase its effect. If you are consuming grapefruit juice, your doctor should monitor for possible adverse effects.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take DILADEL if you are pregnant, planning a pregnancy, or are a woman of childbearing age not using contraceptive medication.
Do not take this medicine if you are breastfeeding, as it passes into breast milk.
If you need to take DILADEL, discontinue breastfeeding.
Driving and using machines
This medicine may affect your ability to drive or operate machinery, as it may cause adverse effects such as malaise and dizziness. If this occurs, avoid driving or operating machinery.
DILADEL contains castor oil
This medicine contains castor oil, which may cause gastrointestinal disturbances and diarrhoea.
DILADEL contains lactose
This medicine contains a type of sugar called lactose. If your doctor has diagnosed you with an intolerance to certain sugars, consult them before taking this medicine.

3. How to take DILADEL

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Treatment of angina pectoris: the recommended dose is 1 tablet three times a day, at regular intervals. If necessary, your doctor may decide to increase the dose to 2 tablets three times a day, depending on your condition.

Treatment of high blood pressure (hypertension): the recommended dose ranges from half a tablet to 1 tablet three times a day.

Use in children
The use of DILADEL is not recommended in children.

Use in elderly patients and patients with kidney or liver problems
If you are elderly or have liver or kidney problems, or are taking other medicines for high blood pressure, the recommended starting dose is half a tablet three times a day.

If you take more DILADEL than you should
Symptoms of overdose include: lowering of blood pressure up to collapse, slowing of the heart rate (bradycardia), and other heart problems (atrio-ventricular conduction disturbances), reduced kidney function.

In case of accidental ingestion or intake of an excessive dose of DILADEL, immediately inform your doctor or go to the nearest hospital emergency department.

If you forget to take DILADEL
If you forget to take a tablet, take it as soon as you remember, unless it is almost time for your next dose. Do not take a double dose to make up for the forgotten dose.

If you stop taking DILADEL
Do not stop treatment with this medicine abruptly, as this may worsen heart problems such as angina. Consult your doctor before stopping treatment.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:

Very common (may affect more than 1 in 10 people)

• swelling due to fluid accumulation (peripheral edema).

Common (may affect up to 1 in 10 people)

• headache (cephalalgia), dizziness;
• serious heart problems such as atrioventricular block, palpitations;
• hot flushes;
• constipation, indigestion, stomach pain, nausea;
• skin irritations such as redness (erythema);
• general malaise.

Uncommon (may affect up to 1 in 100 people)

• nervousness, insomnia;
• slowing of the heartbeat (bradycardia);
• dizziness when standing up, due to a drop in blood pressure (orthostatic hypotension);
• vomiting, diarrhoea;
• liver disorders with changes in liver blood tests, such as increased aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH).

Rare (may affect up to 1 in 1,000 people)

• nosebleeds (epistaxis);
• memory problems (amnesia), depression, personality changes, hallucinations, drowsiness;
• altered sensation in limbs (paraesthesiae), ringing in the ears (tinnitus), tremor;
• chest pain (angina), irregular heartbeat (arrhythmia) which may lead to loss of consciousness (syncope);
• dry mouth, altered taste, abdominal pain;
• changes in blood tests such as increased creatine phosphokinase (CPK);
• loss of appetite (anorexia), weight gain;
• increased need to urinate (polyuria), including during night-time rest (nocturia);
• skin irritations such as hives, generalized redness (erythema) due to blood vessel disorders (leukocytoclastic vasculitis), small hemorrhages under the skin (petechiae), itching;
• bone and joint pain;
• visual disturbances (amblyopia) and eye irritation;
• breathing difficulties (dyspnoea);
• reduced sexual function (impotence).

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

• kidney problems such as interstitial nephritis;
• decrease in the number of white blood cells (leucopenia).

Frequency not known (cannot be estimated from the available data)

• decrease in certain blood cells (platelets) and blood clotting disorders (prolonged bleeding time);
• mood changes (including depression);
• appearance of abnormal movements affecting gait (extrapyramidal syndrome), dizziness;
• heart problems (sinoatrial block), severe decrease in heart function (congestive heart failure), changes in electrocardiogram results, temporary cessation of cardiac impulse formation at the sinus node (sinus arrest), and cardiac arrest due to absence of contraction phase (asystole);
• low blood pressure (hypotension), slowed heart rate (bradycardia), and other heart problems (atrioventricular block at the nodal level) if the medicine is administered intravenously;
• fluid retention (edema), especially in the lower limbs;
• sweating;
• increased gum size (gingival hyperplasia);
• liver inflammation (hepatitis);
• increased blood sugar levels (hyperglycaemia);
• skin disorders due to light sensitivity (including lichenoid keratosis in sun-exposed skin areas);
• swelling of the skin and mucous membranes (angioneurotic edema);
• various skin diseases with redness, blisters, peeling, pustules, sweating, sometimes accompanied by fever (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, acute generalized exanthematous pustulosis, desquamative erythema with or without fever);
• breast enlargement in men (gynaecomastia);
• reduced muscle strength (asthenia);
• bronchial constriction (bronchospasm), including worsening of asthma;
• a condition in which the body's immune system attacks normal tissues, causing symptoms such as joint swelling, fatigue, and skin rashes (called "lupus-like syndrome").

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 http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store DILADEL

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 carton after “exp.”.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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. Package contents and other information

What DILADEL contains

• The active substance is diltiazem hydrochloride. One tablet contains 60 mg of diltiazem hydrochloride.
• The other components are: lactose, hydrogenated castor oil, macrogol 6000 and magnesium stearate.

Description of the appearance of DILADEL and contents of the pack
Carton containing 50 modified-release divisible tablets.
Marketing Authorization Holder
Zentiva Italia S.r.l. – Via P. Paleocapa 7 – 20121 Milan, Italy
Manufacturer
Sanofi Winthrop Industrie 30-36, Avenue Gustave Eiffel, Tours (France)

Patient information leaflet: information for the patient

DILADEL 120 mg prolonged-release tablets

Diltiazem 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 others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

2. What DILADEL is and what it is used for

DILADEL contains the active substance diltiazem hydrochloride, which belongs to a group of medicines called calcium channel blockers (calcium antagonists), used to treat high blood pressure.
DILADEL is indicated for the treatment of:

• chest pain (angina pectoris) due to physical exertion, heart attack, or problems with the arteries supplying blood to the heart (Prinzmetal's angina);
• mild to moderate high blood pressure.

2. What you should know before taking DILADEL

Do not take DILADEL

• if you are allergic to diltiazem or to any of the other ingredients of this medicine (listed in section 6);
• if you have low blood pressure (systolic pressure below 90 mmHg);
• if you have acute myocardial infarction with lung complications;
• if you have an irregular heartbeat due to certain heart diseases (sino-atrial node syndrome, atrioventricular block, sino-atrial block) and do not have a functioning pacemaker;
• if you have a very slow heartbeat (severe bradycardia, less than 40 beats per minute);
• if you have severe heart problems, possibly with lung complications (left ventricular failure with pulmonary congestion and congestive heart failure);
• if you are using medicines such as dantrolene and amiodarone by infusion (see section “Other medicines and DILADEL”);
• if you are using a medicine containing ivabradine for the treatment of certain heart conditions;
• if you are using a medicine containing lomitapide, used to treat high cholesterol levels (see section “Other medicines and DILADEL”);
• if you are pregnant or suspect you may be pregnant, if you are breastfeeding, or if you are a woman of childbearing potential and are not using contraceptive medication to prevent pregnancy.

Warnings and precautions
Talk to your doctor or pharmacist before taking DILADEL.
Speak with your doctor if you have a history of heart failure, unusual shortness of breath, slow heartbeat, or low blood pressure. Cases of kidney damage have been reported in patients with these conditions; your doctor may need to monitor your kidney function.
Use this medicine with great caution and inform your doctor in the following cases:

• if you have heart problems such as reduced left ventricular function, slow heartbeat (bradycardia), or other heart disorders (first-degree atrioventricular block);
• if you are elderly or have kidney or liver problems;
• if you are also taking other medicines that lower blood pressure, as your blood pressure could drop excessively (see “Other medicines and DILADEL”);
• if you are at risk of intestinal obstruction, since diltiazem affects intestinal function; if you are undergoing surgery, inform the anaesthetist that you are taking this medicine.

In the situations listed above, you may be prescribed different doses than those normally used.
Your doctor will perform periodic checks of your heart, liver, and kidney function (during and especially at the beginning of treatment), and of your blood sugar levels if you have diabetes mellitus, as there is a risk of increased blood glucose.
Calcium antagonists, such as diltiazem, may be associated with mood changes, including depression.
During treatment with this medicine, you may notice parts of the tablets in your stools. This is normal and does not indicate lack of effectiveness of the medicine.
The use of DILADEL may cause bronchoconstriction (bronchospasm), including worsening of asthma, particularly in patients who already have breathing difficulties or after dose increases. During DILADEL therapy, your doctor will monitor your respiratory function.
Children
This medicine is not recommended for children.
Other medicines and DILADEL
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not use this medicine in combination with:

• dantrolene (infusion), a medicine used for muscle spasms and for treating a type of fever called malignant hyperthermia;
• amiodarone, a medicine used to treat certain heart conditions;
• medicines containing lomitapide, used to treat high cholesterol levels. Diltiazem can increase lomitapide concentration, which may increase the likelihood and severity of liver-related adverse effects.

Use particular caution and inform your doctor if you are taking any of the following medicines (in some cases, your doctor may adjust the dose of diltiazem or of the other medicines):

• antihypertensives, medicines that reduce blood pressure. If you are taking this medicine together with an antihypertensive, your doctor will closely monitor your blood pressure;
• nitrates, medicines that dilate blood vessels. If you are taking this medicine, nitrates will be prescribed in gradually increasing doses;
• theophylline, a medicine used to treat asthma;
• beta-blockers, medicines used for high blood pressure and heart problems. In this case, your doctor will closely monitor heart function, especially at the beginning of treatment. An increased risk of depression has been reported when diltiazem is administered together with beta-blockers (see section 4);
• medicines for heart conditions in general, and particularly cardiac glycosides (e.g. digoxin). Be especially careful if you are elderly or taking high doses of diltiazem;
• medicines used for heart rhythm disorders (antiarrhythmics). In this case, your doctor will closely monitor your heart function;
• carbamazepine and phenytoin, medicines used for epilepsy. In this case, your doctor will monitor blood levels of carbamazepine and phenytoin;
• rifampicin, a medicine for bacterial infections (antibiotic);
• medicines used for stomach ulcers, known as H2-antagonists, such as cimetidine and ranitidine. If treatment with these medicines is started or stopped during DILADEL treatment, your doctor may adjust the dose of DILADEL;
• cyclosporine, a medicine used to prevent organ transplant rejection;
• medicines for depression (antidepressants) such as imipramine and tricyclic antidepressants;
• medicines used for mental disorders (antipsychotics), including lithium;
• medicines used for anaesthesia (see section “Warnings and precautions”);
• contrast agents for X-ray examinations, as they may enhance the effects of diltiazem on the heart, such as lowering blood pressure;
• antiplatelet agents, medicines that prevent aggregation of certain blood cells called platelets, thereby increasing blood fluidity;
• benzodiazepines, medicines for depression, such as midazolam, triazolam, since diltiazem increases blood concentrations of these drugs;
• corticosteroids, medicines used to treat inflammation. Your doctor will monitor you and adjust the corticosteroid dose if necessary;
• statins, medicines used to lower blood cholesterol, as there may be a risk of serious muscle damage (myopathy and rhabdomyolysis); cilostazol, a medicine used to relieve leg pain during walking. DILADEL increases the activity of cilostazol.

DILADEL and beverages
Avoid taking this medicine with grapefruit juice, as it may increase its effect. If you are consuming grapefruit juice, your doctor should monitor you for possible adverse effects.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take DILADEL if you are pregnant, planning a pregnancy, or if you are a woman of childbearing potential not using contraceptive medication to prevent pregnancy.
Do not take this medicine if you are breastfeeding, as this medicine passes into breast milk.
If you need to take DILADEL, discontinue breastfeeding.
Driving and using machines
This medicine may affect your ability to drive or operate machinery, as it may cause adverse effects such as malaise and dizziness. If this occurs, avoid driving or operating machinery.
DILADEL contains sucrose
This medicine contains sucrose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take DILADEL

Take this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Treatment of angina pectoris and high blood pressure: the recommended dose is 1 tablet every
12 hours.
This medicine is intended for maintenance therapy.
Do not chew the tablets; swallow them whole with some water.
Use in children
DILADEL is not recommended for use in children.
Use in elderly patients and patients with kidney or liver problems
If you are elderly or have liver or kidney problems, or are taking other medicines for high blood pressure, the recommended initial dose is the lowest effective dose.
If you take more DILADEL than you should
Symptoms of overdose include: low blood pressure up to collapse,
slowing of the heartbeat (bradycardia), and other heart problems (atrio-ventricular conduction disorders), reduced kidney function.
In case of accidental ingestion/overdose of DILADEL, contact your doctor immediately or go to the Emergency Department of the nearest hospital.
If you forget to take DILADEL
If you forget to take a tablet, take it as soon as you remember, unless it is almost time for your next dose. Do not take a double dose to make up for the missed dose.
If you stop taking DILADEL
Do not stop treatment with this medicine abruptly, as this may worsen heart conditions such as angina. Consult your doctor before stopping treatment.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:

Very common (may affect more than 1 in 10 people)

• swelling due to fluid accumulation (peripheral oedema).

Common (may affect up to 1 in 10 people)

• headache (cephalalgia), dizziness;
• serious heart problems such as atrioventricular block, palpitations;
• hot flushes;
• constipation, digestive disorders, stomach pain, nausea;
• skin irritations such as redness (erythema);
• general malaise.

Uncommon (may affect up to 1 in 100 people)

• nervousness, insomnia;
• slowing of the heartbeat (bradycardia);
• sensation of dizziness when standing up due to a drop in blood pressure (orthostatic hypotension);
• vomiting, diarrhoea;
• liver disorders with changes in liver blood tests, such as increased aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH).

Rare (may affect up to 1 in 1,000 people)

• nosebleeds (epistaxis);
• memory problems (amnesia), depression, personality changes, hallucinations, drowsiness;
• altered sensation in limbs (paraesthesiae), ringing in the ears (tinnitus), tremor;
• chest pain (angina), irregular heartbeat (arrhythmia) which may lead to loss of consciousness (syncope);
• dry mouth, altered taste, abdominal pain;
• changes in blood tests such as increased creatine phosphokinase (CPK);
• loss of appetite (anorexia), weight gain;
• increased need to urinate (polyuria), including during night-time rest (nocturia);
• skin irritations such as hives, widespread redness (erythema) due to blood vessel disorders (leucocytoclastic vasculitis), small skin haemorrhages (petechiae), itching;
• bone and joint pain;
• vision disturbances (amblyopia) and eye irritation;
• breathing difficulties (dyspnoea);
• reduced sexual function (impotence).

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

• kidney problems such as interstitial nephritis;
• decrease in the number of white blood cells (leucopenia).

Frequency not known (cannot be estimated from the available data)

• decrease in certain blood cells (platelets) and blood clotting disorders (prolonged bleeding time);
• mood changes (including depression);
• development of abnormal movements affecting gait (extrapyramidal syndrome), dizziness;
• heart problems (sino-atrial block), severe reduction in heart function (congestive heart failure), changes in electrocardiogram results, temporary interruption of cardiac impulse formation at the sinus node level (sinus arrest), and cardiac arrest due to absence of contraction phase (asystole);
• low blood pressure (hypotension), slowed heart rate (bradycardia), and other heart problems (atrioventricular block at nodal level) if the medicine is administered intravenously;
• fluid retention (oedema), particularly in the lower limbs;
• sweating;
• increased gum size (gingival hyperplasia);
• liver inflammation (hepatitis);
• increased blood sugar levels (hyperglycaemia);
• skin disorders due to light sensitivity (including lichenoid keratosis in sun-exposed skin areas);
• swelling of the skin and mucous membranes (angioneurotic oedema);
• various skin diseases with redness, blisters, peeling, pustules, sweating, sometimes accompanied by fever (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, generalised acute exanthematous pustulosis, desquamative erythema with or without fever);
• breast enlargement in men (gynaecomastia);
• reduced muscle strength (asthenia);
• bronchial constriction (bronchospasm), including worsening of asthma;
• a condition in which the body's immune system attacks normal tissues, causing symptoms such as joint swelling, fatigue, and skin rashes (called "lupus-like syndrome").

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://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 DILADEL

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 packaging after "exp.".
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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. Package contents and other information

What DILADEL contains

• The active substance is diltiazem hydrochloride. One tablet contains 120 mg of diltiazem hydrochloride.
• The other components are:
  Tablet core: monobasic sodium citrate, sucrose, povidone, macrogol 6000 and magnesium stearate.
  Tablet coating: sucrose, modified PVC, acetylbutyl citrate, sodium bicarbonate, ethyl vanillin, titanium dioxide (E171).

Description of the appearance of DILADEL and package contents
Carton pack containing 24 prolonged-release tablets.
Marketing Authorization Holder
Zentiva Italia S.r.l. – Via P. Paleocapa 7 – 20121 Milano
Manufacturer
Sanofi Winthrop Industrie, 30-36 Avenue Gustave Eiffel, Tours (France)
Package leaflet: information for the patient

DILADEL 200 mg prolonged-release hard capsules, 300 mg prolonged-release hard capsules

Diltiazem 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 others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What DILADEL is and what it is used for

DILADEL contains the active substance diltiazem hydrochloride, which belongs to a group of medicines called calcium channel blockers (calcium antagonists), used to treat high blood pressure.
DILADEL is indicated for the treatment of:

• chest pain (angina pectoris) due to physical exertion, a heart attack, or problems with the arteries supplying blood to the heart (Prinzmetal's angina);
• mild to moderate high blood pressure.

2. What you should know before taking DILADEL

Do not take DILADEL

• if you are allergic to diltiazem or to any of the other ingredients of this medicine (listed in section 6);
• if you have low blood pressure (systolic pressure below 90 mmHg);
• if you have acute heart attack with lung complications;
• if you have an irregular heartbeat due to certain heart conditions (sino-atrial node syndrome, atrioventricular block, sino-atrial block) and do not have a functioning pacemaker;
• if you have a very slow heart rate (severe bradycardia, less than 40 beats per minute);
• if you have severe heart problems, possibly with lung complications (left ventricular failure with pulmonary congestion and congestive heart failure);
• if you are using medicines such as dantrolene and amiodarone by infusion (see section “Other medicines and DILADEL”);
• if you are using a medicine containing ivabradine for the treatment of certain heart conditions;
• if you are using a medicine containing lomitapide, used to treat high cholesterol levels (see section “Other medicines and DILADEL”);
• if you are pregnant or suspect you may be pregnant, if you are breastfeeding, or if you are a woman of childbearing age and are not using medicines to prevent pregnancy (contraceptives).

Warnings and precautions
Talk to your doctor or pharmacist before taking DILADEL.
Speak with your doctor if you have a history of heart failure, unusual shortness of breath, slow heartbeat, or low blood pressure. Cases of kidney damage have been reported in patients with these conditions; your doctor may need to monitor your kidney function.
Use this medicine with great caution and inform your doctor in the following cases:

• if you have heart problems such as reduced left ventricular function, slow heart rate (bradycardia), or other heart disorders (first-degree atrioventricular block);
• if you are elderly or have kidney or liver problems;
• if you are also taking other medicines that lower blood pressure, as blood pressure could drop excessively (see “Other medicines and DILADEL”);
• if you are at risk of intestinal obstruction, since diltiazem affects intestinal function;
• if you are undergoing surgery; in this case, inform the anaesthetist that you are taking this medicine.

In the cases listed above, you may be prescribed different doses than those normally used.
Your doctor will periodically check your heart, liver, and kidney function (during and especially at the beginning of treatment), and your blood sugar levels if you have diabetes mellitus, as there is a risk of increased blood glucose.
Calcium antagonists, such as diltiazem, may be associated with mood changes, including depression.
The use of DILADEL may cause bronchoconstriction (bronchospasm), including worsening of asthma, particularly in patients who already have breathing difficulties or after dose escalation. During treatment with DILADEL, your doctor will monitor your respiratory function.

Children
This medicine is not recommended for children.

Other medicines and DILADEL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Do not use this medicine in combination with:

• dantrolene (infusion), a medicine used for muscle spasms and for treating a type of fever called malignant hyperthermia;
• amiodarone, a medicine used to treat certain heart conditions;
• medicines containing lomitapide, used to treat high cholesterol levels. Diltiazem can increase lomitapide concentration, which may lead to an increased likelihood and severity of liver-related adverse effects.

Use special caution and inform your doctor if you are taking any of the following medicines (in some cases, your doctor may adjust the dose of diltiazem or of the other medicines):

• antihypertensives, medicines that reduce blood pressure. If you are taking this medicine together with an antihypertensive, your doctor will closely monitor your blood pressure;
• nitrates, medicines that dilate blood vessels. If you are taking this medicine, nitrates will be prescribed at gradually increasing doses;
• theophylline, a medicine used for asthma treatment;
• beta-blockers, medicines used for high blood pressure and heart problems. In this case, your doctor will closely monitor heart function, especially at the beginning of treatment. An increased risk of depression has been reported when diltiazem is administered together with beta-blockers (see section 4);
• medicines for heart conditions in general, and particularly cardioactive glycosides (e.g., digoxin). Exercise particular caution, especially if you are elderly or taking high doses of diltiazem;
• medicines used for heart rhythm disorders (antiarrhythmics). In this case, your doctor will closely monitor your heart function;
• carbamazepine and phenytoin, medicines used for epilepsy. In this case, your doctor will monitor blood levels of carbamazepine and phenytoin;
• rifampicin, a medicine for bacterial infections (antibiotic);
• medicines used for stomach ulcers known as H2-antagonists, such as cimetidine and ranitidine. If treatment with these medicines is started or stopped during DILADEL treatment, your doctor may adjust the dose of diltiazem;
• cyclosporine, a medicine used to prevent organ transplant rejection;
• medicines used for depression (antidepressants) such as imipramine and tricyclic antidepressants;
• medicines used for mental disorders (antipsychotics), including lithium;
• medicines used for anaesthesia (see section “Warnings and precautions”);
• contrast media for X-ray examinations, as they may enhance the heart-related effects of diltiazem, such as lowering of blood pressure;
• antiplatelet agents, medicines that prevent aggregation of certain blood cells called platelets, thereby increasing blood fluidity;
• benzodiazepines, medicines for depression, such as midazolam and triazolam, since diltiazem increases blood concentrations of these drugs;
• corticosteroids, medicines used to treat inflammation. Your doctor will monitor you and adjust the corticosteroid dose if necessary;
• statins, medicines used to lower blood cholesterol; because there may be a risk of serious muscle damage (myopathy and rhabdomyolysis);
• cilostazol, a medicine used to relieve leg pain when walking. DILADEL increases the activity of cilostazol.

DILADEL with food and drinks
Avoid taking this medicine with grapefruit juice, as it may increase its effect. If you are consuming grapefruit juice, your doctor should monitor for possible adverse effects.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take DILADEL if you are pregnant, planning a pregnancy, or if you are a woman of childbearing age not using medicines to prevent pregnancy (contraceptives).
Do not take this medicine if you are breastfeeding, as this medicine passes into breast milk.
If you need to take DILADEL, discontinue breastfeeding.

Driving and using machines
This medicine may affect your ability to drive and use machinery because it may cause adverse effects such as malaise and dizziness. If this occurs, avoid driving or operating machinery.

3. How to take DILADEL

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Treatment of angina pectoris and high blood pressure: the recommended starting dose is 1 capsule of 200 mg daily. If necessary, your doctor may decide to increase the dose to 1 capsule of 300 mg daily, depending on your condition.
This medicine is intended for maintenance therapy.
Do not chew the capsules; swallow them whole with a little water, preferably before or during a meal, consistently.
Use in children
The use of DILADEL is not recommended in children.
Use in elderly people and those with kidney or liver problems
If you are elderly or have liver or kidney problems, or are taking other medicines for high blood pressure, the recommended starting dose is 1 capsule of 200 mg daily.
If you take more DILADEL than you should
Symptoms of overdose include: lowering of blood pressure up to collapse, slowing of the heartbeat (bradycardia), and other heart problems (atrio-ventricular conduction disturbances), reduced kidney function.
In case of accidental ingestion or intake of an excessive dose of DILADEL, immediately inform your doctor or go to the Emergency Department of the nearest hospital.
If you forget to take DILADEL
If you forget to take a capsule, take it as soon as you remember, unless it is almost time for your next dose. Do not take a double dose to make up for the missed dose.
If you stop taking DILADEL
Do not stop treatment with this medicine abruptly, as this may worsen heart conditions such as angina. Consult your doctor before stopping treatment.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The following side effects may occur:

Very common (may affect more than 1 in 10 people)

• swelling due to fluid accumulation (peripheral edema).

Common (may affect up to 1 in 10 people)

• headache (cephalalgia), dizziness;
• serious heart problems such as atrioventricular block, palpitations;
• hot flushes;
• constipation, digestive disturbances, stomach pain, nausea;
• skin irritations such as redness (erythema);
• general malaise.

Uncommon (may affect up to 1 in 100 people)

• nervousness, insomnia;
• slowing of the heart rate (bradycardia);
• dizziness upon standing due to a drop in blood pressure (orthostatic hypotension);
• vomiting, diarrhoea;
• liver problems with abnormal liver blood tests, such as increased aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH).

Rare (may affect up to 1 in 1,000 people)

• nosebleeds (epistaxis);
• memory problems (amnesia), depression, personality changes, hallucinations, drowsiness;
• altered sensation in limbs (paraesthesiae), ringing in the ears (tinnitus), tremor;
• chest pain (angina), irregular heartbeat (arrhythmia) which may lead to loss of consciousness (syncope);
• dry mouth, altered taste, abdominal pain;
• abnormal blood tests such as increased creatine phosphokinase (CPK);
• loss of appetite (anorexia), weight gain;
• increased need to urinate (polyuria), including during night-time rest (nocturia);
• skin irritations such as hives, generalized redness (erythema) due to blood vessel disorders (leukocytoclastic vasculitis), small hemorrhages under the skin (petechiae), itching;
• bone and joint pain;
• visual disturbances (amblyopia), eye irritation;
• breathing difficulties (dyspnoea);
• reduced sexual function (impotence).

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

• kidney problems such as interstitial nephritis;
• decrease in the number of white blood cells (leucopenia).

Frequency not known (frequency cannot be estimated from the available data)

• decrease in certain blood cells (platelets) and abnormalities in blood clotting (prolonged bleeding time);
• mood changes (including depression);
• onset of abnormal movements affecting gait (extrapyramidal syndrome), dizziness;
• heart problems (sinoatrial block), severe reduction in heart function (congestive heart failure), changes in electrocardiogram results, temporary cessation of cardiac impulse formation at the sinus node level (sinus arrest), and cardiac arrest due to absence of contraction phase (asystole);
• low blood pressure (hypotension), slowed heart rate (bradycardia), and other heart problems (atrioventricular block at the nodal level) if the medicine is administered intravenously;
• fluid retention (edema), particularly in the lower limbs;
• sweating;
• enlargement of the gums (gingival hyperplasia);
• inflammation of the liver (hepatitis);
• increased blood sugar levels (hyperglycaemia);
• skin disorders due to light sensitivity (including lichenoid keratosis in sun-exposed skin areas);
• swelling of the skin and mucous membranes (angioneurotic edema);
• various skin diseases with redness, blisters, peeling, pustules, sweating, sometimes accompanied by fever (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, acute generalized exanthematous pustulosis, desquamative erythema with or without fever);
• breast enlargement in men (gynaecomastia);
• reduced muscle strength (asthenia);
• bronchial constriction (bronchospasm), including worsening of asthma;
• a condition in which the body's immune system attacks normal tissues, causing symptoms such as joint swelling, fatigue, and skin rashes (called "lupus-like syndrome").

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 http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store DILADEL

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 carton after “exp.”.
The expiry date refers to the last day of that month.
Store this medicine at a temperature not exceeding 30°C.
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 DILADEL contains
DILADEL 200 mg prolonged-release hard capsules
Each capsule contains a mixture of immediate-release and prolonged-release microgranules.

• The active substance is diltiazem hydrochloride. One capsule contains 200 mg of diltiazem hydrochloride.
• The other components are: microcrystalline cellulose, sodium carmellose, acrylic and methacrylic acid copolymer esters, ethylcellulose, diacetylated monoglycerides and magnesium stearate. Capsule shell composition: gelatin, titanium dioxide (E171), iron oxides (E172).

DILADEL 300 mg prolonged-release hard capsules
Each capsule contains a mixture of immediate-release and prolonged-release microgranules.

• The active substance is diltiazem hydrochloride. One capsule contains 300 mg of diltiazem hydrochloride.
• The other components are: microcrystalline cellulose, sodium carmellose, acrylic and methacrylic acid copolymer esters, ethylcellulose, diacetylated monoglycerides and magnesium stearate. Capsule shell composition: gelatin, titanium dioxide (E171), iron oxides (E172).

Description of the appearance of DILADEL and contents of the pack
DILADEL 200 mg prolonged-release hard capsules
Carton pack containing 36 capsules.
DILADEL 300 mg prolonged-release hard capsules
Carton pack containing 14 capsules.
Marketing Authorization Holder
Zentiva Italia S.r.l. – Via P. Paleocapa 7 – 20121 Milano
Manufacturer
Sanofi Winthrop Industrie 30-36, Avenue Gustave Eiffel, Tours (France)
Delpharm Dijon, 6 Boulevard De L’Europe, Quétigny (France)