CHIARO 250 mg Coated Tablet

Зміст інструкції

1. Chiaro 250 mg coated tablets
   1. What Chiaro is and what it is used for
   2. What you need to know before taking Chiaro
   3. How to use Chiaro
   4. Possible side effects
   5. How to store Chiaro
   6. Contents of the pack and other information

Chiaro 250 mg coated tablets

Ticlopidine hydrochloride

Read this leaflet carefully before you start 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 or pharmacist.
• 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 you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Chiaro is and what it is used for

Chiaro contains the active ingredient ticlopidine hydrochloride and belongs to a group of medicines called
“antithrombotics and antiplatelet agents”.
Ticlopidine is a medicine that inhibits platelet aggregation (corpuscles present in the blood),
preventing the formation of thrombi (blood clots).
Chiaro is indicated in the prevention of the formation of circulating blood clots that can obstruct the
blood vessels of the heart and brain (occlusive cerebro and cardiovascular ischemic events), in people at
risk of thrombosis and in particular in the following clinical conditions:

• narrowing or obstruction of the arteries that reduces blood flow to the legs (peripheral obliterating arteriopathy);
• previous myocardial infarction;
• previous cases of transient and recurrent loss of certain brain functions, caused by a reduction in blood flow to the brain (recurrent transient ischemic attacks);
• cerebrovascular lesion caused by interruption of blood flow to the brain due to obstruction of an artery (ischemic stroke);
• presence of chest pain at rest caused by the formation of a clot and constriction of the coronary artery muscles (unstable angina).

Chiaro is also indicated:

• in the prevention of re-occlusion of cardiac bypasses (aorto-coronary);
• in extracorporeal circulation (a technique that allows the temporary replacement of the heart and lungs with a machine that replaces their functions);
• in hemodialysis (a method most frequently used to treat kidney failure);
• in thrombosis of the central retinal vein. If you have had a previous myocardial infarction and a transient ischemic attack, your doctor will prescribe Chiaro only if you cannot be treated with acetylsalicylic acid (ASA) or ASA has already proven ineffective.

2. What you need to know before taking Chiaro

Do not take Chiaro if:

• you are allergic to the active ingredient or to any of the other ingredients of this medicine (listed in section 6);
• you suffer from or have previously suffered from a decrease in the number of white blood cells, platelets and granulocytes (leukopenia, thrombocytopenia and agranulocytosis) in the blood;
• you have a predisposition to the development of bleeding (bleeding diathesis) previous or current and blood diseases (haemopathies) that involve a prolongation of bleeding time;
• you have organic lesions susceptible to bleeding, such as ulcers of the gastrointestinal tract, or dilation of the veins of the esophagus (esophageal varices), etc.;
• you have active lesions of a cerebral artery, with consequent blood loss into the brain (acute hemorrhagic stroke);
• you suffer from severe liver diseases (severe hepatopathies);
• you are already taking medicines potentially harmful to the bone marrow (myelotoxic medicines), which cause a reduction in the production of white and red blood cells (see section “Other medicines and Chiaro”);
• you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”).

In some cases, a decrease in white blood cells or
agranulocytosis has been reported during treatment with ticlopidine, sometimes even with irreversible consequences, therefore your doctor will prescribe Chiaro only in cases where it cannot be replaced with other medicines.
Chiaro must absolutely not be used in primary prevention in clinically healthy people.

Warnings and precautions
Talk to your doctor or pharmacist before taking Chiaro if:

• you have an increased risk of developing bleeding;
• you suffer from liver disorders (confirmed or suspected), as in this case the doctor will subject you to tests to assess your liver function, especially during the first months of treatment with Chiaro;
• you suffer from kidney problems (renal insufficiency). The doctor will assess whether to reduce the dose of Chiaro and will advise you to stop treatment if hematological and bleeding problems should occur.

Immediately inform your doctor if you experience any of the following symptoms, as treatment with Chiaro must be stopped:

• signs and symptoms that may be related to neutropenia, i.e. a reduction in the number of neutrophils in the blood, such as: fever, sore throat, oral ulcers;
• signs and symptoms that may be related to thrombocytopenia, i.e. a reduction in the number of platelets in the blood, and/or blood coagulation disorders (haemostasis), such as: prolonged or unexpected bleeding, presence of bruises on the body (ecchymoses), presence of spots on the body associated with bleeding (purpura), dark stools;
• signs and symptoms that may be related to acute and severe diseases of small blood vessels, which damage platelets and red blood cells (thrombotic thrombocytopenic purpura), such as: thrombocytopenia, low hemoglobin concentration in the blood due to excessive destruction of red blood cells and insufficient bone marrow response (hemolytic anemia), neurological symptoms similar to those of a transient ischemic attack or stroke, kidney disorders and fever. The onset of thrombotic thrombocytopenic purpura can be sudden, more likely within the first 8 weeks of starting treatment with Chiaro, and the risk of fatal outcome is high;
• liver inflammation with destruction of cells and tissues and/or with blockage of the bile ducts (cytolytic and/or cholestatic hepatitis), especially during the first months of treatment. If you experience symptoms of hepatitis such as jaundice, dark urine, and pale stools, inform your doctor immediately, who will advise you to stop treatment with Chiaro and undergo liver function tests;
• diarrhea associated with inflammation of the colon (colitis), including colitis with an increase in the number of lymphocytes within the lining of the colon (lymphocytic colitis). If the effect is severe and persistent, your doctor will advise you to stop treatment with Chiaro.

The doctor will assess whether to have you resume or not the treatment with Chiaro based on the results of clinical and laboratory tests.

It is possible that during treatment with Chiaro you may experience:

• manifestation of undesirable effects, sometimes serious and fatal, of a hematological and bleeding nature, such as a reduction in the level of granulocytes (agranulocytosis), a reduction in the number of all blood cells (pancytopenia) and, in rare cases, the onset of a cancer affecting white blood cells (leukemia). These serious undesirable effects may be due to:
• inadequate medical control, late diagnosis and inappropriate treatment of undesirable effects;
• concomitant administration of other anticoagulants or substances that inhibit platelet aggregation (antiplatelet agents) such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) (see section “Other medicines and Chiaro”). It is therefore necessary that you strictly adhere to the instructions provided by your doctor;
• a reduction, beyond normal limits, in the number of white blood cells and platelets. For this reason, your doctor will advise you to undergo a complete examination for the evaluation of the number of these blood cells (complete hemocytometric examination), with determination of the number and characteristics of the different groups of white blood cells (differential leukocyte count) and determination of the number of platelets (platelet count). You must undergo these tests, under medical supervision, at the beginning of treatment with Chiaro and every 2 weeks for the first three months. In addition, if you interrupt treatment with Chiaro within the first 3 months for any reason, your doctor will advise you to undergo these tests 2 weeks after stopping treatment. If the blood tests confirm a too low level in the blood of neutrophils (a type of white blood cells) or platelets, your doctor will advise you to stop treatment with Chiaro and monitor your hemocytometric parameters until they return to normal values.
• an increased risk of developing bleeding, therefore it is necessary to take some measures in case of surgical interventions:
• in case of minor surgical interventions (e.g. tooth extraction), inform your doctor and dentist that you are taking Chiaro;
• before a scheduled surgical intervention, your doctor will advise you to stop treatment with Chiaro at least 10 days before (except in cases where antithrombotic activity is expressly required); after stopping treatment, the medical staff will assess the possible persistence of the effect on bleeding time before proceeding with the intervention;
• in case of emergency surgery, the medical staff will assess the method to be adopted to limit the risk of bleeding and prolonged bleeding time;
• increased levels of high and low density lipoproteins (HDL-C, LDL-C, VLDL-C) and fats (triglycerides) in the blood, which usually occurs after 1-4 months of treatment;
• diarrhea generally mild and transient, which occurs mostly during the first three months of treatment and which usually resolves within 1-2 weeks without the need to stop treatment with Chiaro;
• irritation and swelling of the skin (skin rashes) mostly observed during the first three months of treatment and which resolve within a few days of stopping treatment.

Pay attention to the use of Chiaro if you are allergic to other medicines similar to ticlopidine (medicines
belonging to the thienopyridine group), such as clopidogrel and prasugrel, because cross-reactions may occur (See section 4). Taking these medicines may cause allergic reactions from moderate to severe such as skin irritation (rash), swelling of the face, especially around the eyes
and mouth (angioedema or Quincke's edema), alteration of the levels of platelets and white blood cells in
the blood (thrombocytopenia and neutropenia).
Patients who have experienced an allergy to a thienopyridine may have a higher risk of
experiencing the same or another reaction to another thienopyridine. It is recommended to check for cross-reactivity
and signs of hypersensitivity in patients with a known allergy to thienopyridines

Children and adolescents
Use in children and adolescents is not recommended due to lack of experience in clinical studies.

Other medicines and Chiaro
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines, including those available without a prescription.
Tell your doctor or pharmacist if you are taking:

• medicines potentially harmful to the bone marrow (myelotoxic medicines), which cause a reduction in the production of white and red blood cells. Administration with Chiaro should be avoided (see section “Do not take Chiaro if”);
• medicines that increase the risk of bleeding, such as:
• non-steroidal anti-inflammatory drugs (NSAIDs);
• antiplatelet agents;
• salicylic acid derivatives (by extrapolation from acetylsalicylic acid). However, if you have had a stent implanted (a device for repairing blocked or damaged arteries), your doctor will advise you to take Chiaro together with aspirin for about a month after implantation;
• oral anticoagulants and heparins. If these medicines are necessary for you, your doctor will subject you to careful clinical and laboratory monitoring;
• theophylline, used for respiratory problems. Your doctor will prescribe blood tests to monitor theophylline plasma levels;
• digoxin, used for heart problems, as the association with Chiaro slightly reduces its levels in the blood;
• phenobarbital and phenytoin, medicines used to treat epilepsy;
• medicines that are eliminated through the liver, as the association with Chiaro increases their residence time in the body. In such cases, the doctor will provide an adjustment of the dose of these medicines, at the beginning and after stopping concomitant administration;
• antacids, as they reduce the level of ticlopidine in the blood;
• cimetidine used in the treatment of gastric ulcer, as it significantly increases the level of ticlopidine in the blood;
• cyclosporine, a medicine used to modulate the body's immune response and prevent transplant rejection, as in very rare cases a reduction in cyclosporine levels in the blood has been reported; the doctor will monitor cyclosporine levels in the blood.
• ketamine, a medicine used in general anesthesia.

You must specifically inform your doctor if you are taking:

• A selective serotonin reuptake inhibitor (including, but not limited to, fluoxetine or fluvoxamine), medicines usually used to treat depression.
• Pentoxifylline, a medicine used for poor blood circulation in the arms and legs.

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

Pregnancy
The safety of ticlopidine in pregnant women has not been established.
Chiaro should not be used during pregnancy unless your doctor considers it absolutely
necessary.

Breastfeeding
The safety of ticlopidine in breastfeeding women has not been established.
Chiaro should not be used during breastfeeding unless your doctor considers it
absolutely necessary.

Driving and using machines
Chiaro may cause side effects that may affect your ability to drive and operate machinery, such as dizziness. Therefore, be careful when driving and using machinery.

Chiaro contains Lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this
medicine.

3. How to use Chiaro

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended dose for long-term therapy is 1 or 2 tablets per day, to be taken during
meals.

Use in children and adolescents
Use in children and adolescents is not recommended due to the lack of experience in clinical
studies.

If you take more Chiaro than you should
In case of ingestion/taking of an excessive dose of Chiaro, contact your doctor immediately or
go to the nearest hospital.
If you take more Chiaro than you should, you are at risk of bleeding.

Treatment method in case of taking an excessive dose of Chiaro
In case of ingestion/taking of an excessive dose of Chiaro, a severe gastrointestinal
intolerance may occur. In this case, in hospital you will undergo induction of vomiting, gastric
lavage and appropriate supportive therapy.
If a rapid correction of prolonged bleeding time is necessary, you will undergo a
platelet transfusion which can reverse the effects of ticlopidine.
Chiaro is not removed through dialysis.

If you forget to take Chiaro
Do not take a double dose to make up for a missed dose.

If you stop taking Chiaro
If you have any doubts 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.

Stop treatment with Chiaro and immediately consult your doctor if during treatment you experience:

• liver disease with destruction of cells and tissues and/or with blockage of the bile ducts (cytolytic and/or cholestatic hepatitis) and persistent and severe cholestatic jaundice (see section “Warnings and precautions”);
• severe diarrhea with colitis, including colitis with an increase in the number of lymphocytes within the lining of the colon (lymphocytic colitis).

The following side effects have been observed with the use of Chiaro:

Common (may affect up to 1 in 10 people):

• reduction in the level of neutrophils in the blood (neutropenia), even severe, and reduction in the level of granulocytes (agranulocytosis) (see section “Warnings and precautions”);
• headache, dizziness;
• diarrhea and feeling unwell (nausea) (see section “Warnings and precautions”);
• increased liver enzymes, increase (isolated or not) in alkaline phosphatase and transaminases (increase of more than two times above the upper limit of normal);
• skin rashes, mostly associated with spots and small lesions or urticaria reactions, often accompanied by itching, which may be widespread (see section “Warnings and precautions”);
• increased levels of cholesterol and triglycerides in the blood (see section “Warnings and precautions”).

Uncommon (may affect up to 1 in 100 people):

• cases of isolated decrease in platelets (thrombocytopenia), in exceptional cases accompanied by a decrease in the number of red blood cells (hemolytic anemia);
• generalized infection of the body (sepsis) with damage to organs and tissues, and septic shock can be fatal complications of agranulocytosis;
• sensory disturbances (peripheral neuropathy);
• bleeding complications, especially bruising (ecchymosis) and nosebleeds (epistaxis), presence of blood in the urine (hematuria) or bleeding of the conjunctiva of the eye, bleeding during and following surgical procedures which may be severe and sometimes with fatal consequences (see section “Warnings and precautions”);
• lesions affecting the inner lining of the stomach and duodenum (gastroduodenal ulcer);
• increased level of bilirubin in the blood;
• skin irritation accompanied by skin flaking (exfoliative dermatitis).

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

• reduction in the number of all blood cells (pancytopenia); marked reduction of the tissue of the bone marrow dedicated to the production of blood cells (bone marrow aplasia); thrombotic thrombocytopenic purpura (an acute blood disease, characterized by the formation of platelet aggregates which, obstructing the vessels, determines a deficiency in the supply of oxygen to the tissues of different organs and, a severe decrease in circulating platelets, which are consumed in forming the aggregates, and anemia (deficiency of circulating hemoglobin)); a form of cancer affecting white blood cells (leukemia); increase in the number of platelets beyond the normal threshold (thrombocytosis) (see section “Warnings and precautions”);
• feeling of discomfort in the ears perceived as whistling or ringing (tinnitus);
• bleeding in the brain caused by the rupture of a blood vessel (intracerebral hemorrhages);
• liver disease with destruction of cells and tissues and/or with blockage of the bile ducts (cytolytic and/or cholestatic hepatitis) and cholestatic jaundice (see section “Warnings and precautions”).

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

• immunological reactions with various manifestations, such as, for example, allergic reactions, increase beyond the threshold of a subpopulation of white blood cells (eosinophilia), severe acute allergic reaction (anaphylaxis), rapid swelling of the skin and subcutaneous tissues (angioedema), joint pain (arthralgia), inflammation of blood vessels (vasculitis), chronic inflammatory disease of connective tissue (lupoid syndrome), allergic lung disorders (allergic pneumopathy), kidney disease on an immunological basis (hypersensitivity nephropathy) sometimes with resulting kidney failure;
• severe diarrhea with colitis, including colitis with an increase in the number of lymphocytes within the lining of the colon (lymphocytic colitis) (see section “Warnings and precautions”);
• cases of fatal and fulminant hepatitis;
• inflammatory disease of the blood vessels of the skin (erythema multiforme), severe disease of the skin and mucous membranes (Stevens-Johnson syndrome), severe skin disease with death of skin cells (Lyell's syndrome);
• fever.

Not known (frequency cannot be estimated from available data):

• cross-reactivity of hypersensitivity between thienopyridines, such as clopidogrel and prasugrel (see section “Warnings and precautions”);
• itching, red skin rash (eczema/dermatitis);
• inflammation of the lungs with cough and difficulty breathing (interstitial lung disease) caused by allergic pneumonia.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through
the address 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 Chiaro

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.
The expiry date indicated refers to the product in intact packaging, correctly stored.
This medicine does not require any particular storage conditions.
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 Chiaro contains

• The active ingredient is ticlopidine hydrochloride. Each Chiaro tablet contains 250 mg of ticlopidine hydrochloride.
• The other ingredients are: corn starch, microcrystalline cellulose, magnesium stearate, precipitated silica, povidone K30, anhydrous lactose, hypromellose, titanium dioxide, polyethylene glycol 6000.

Description of the appearance of Chiaro and contents of the pack
Chiaro is presented in the form of film-coated tablets, contained in blisters.
Each pack contains two blisters of 15 tablets each.

Marketing authorisation holder and manufacturer

Marketing authorisation holder
NEOPHARMED GENTILI S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milano

Manufacturer
Fine Foods & Pharmaceuticals NTM S.p.A.
Via Grignano 43

• 24041 – Brembate (BG)