Chiaro

Italy
Brand name Chiaro
Form tablets, film-coated
Active substance / Dosage
TICLOPIDINE HYDROCHLORIDE
Prescription type Prescription only – non-repeatable
ATC code
B01AC05
Registration number 035319
Manufacturer NEOPHARMED GENTILI S.P.A.

Table of Contents

Patient Information Leaflet

Chiaro 250 mg coated tablets

Ticlopidine hydrochloride
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, ask your doctor 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, contact 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 taking Chiaro
  3. How to take 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 substance ticlopidine hydrochloride and belongs to a group of medicines known as "antithrombotic and antiplatelet agents".
Ticlopidine is a medicine that inhibits platelet aggregation (platelets are blood components), thereby preventing the formation of blood clots (thrombi).
Chiaro is indicated for the prevention of circulating blood clots that may block blood vessels in the heart and brain (occlusive cerebro-cardiovascular ischemic events), in individuals at risk of thrombosis, and particularly in the following clinical conditions:

  • narrowing or blockage of arteries reducing blood flow to the legs (peripheral arterial occlusive disease);
  • previous myocardial infarction;
  • previous episodes of transient and recurrent loss of certain brain functions caused by reduced blood flow to the brain (recurrent transient ischemic attacks);
  • cerebrovascular damage caused by interruption of blood flow to the brain due to blockage of an artery (ischemic stroke);
  • presence of resting chest pain caused by blood clot formation and constriction of the muscle in the coronary arteries (unstable angina).

Chiaro is also indicated:

  • for the prevention of re-occlusion of cardiac bypass grafts (aortocoronary bypass);
  • during extracorporeal circulation (a technique allowing temporary replacement of heart and lung function by a machine);
  • during hemodialysis (a method most frequently used to treat renal failure);
  • in central retinal vein thrombosis.

If you have previously had a myocardial infarction and a transient ischemic attack, your doctor will prescribe Chiaro only if you cannot be treated with acetylsalicylic acid (ASA), or if ASA has proven ineffective.

2. What you must know before taking Chiaro

Do not take Chiaro if:

  • you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
  • you currently suffer or have previously suffered from a reduced number of white blood cells, platelets, or granulocytes (leukopenia, thrombocytopenia, and agranulocytosis) in the blood;
  • you have a predisposition to bleeding (hemorrhagic diathesis), either current or past, or blood disorders (hemopathies) that cause prolonged bleeding time;
  • you have organic lesions prone to bleeding, such as gastrointestinal ulcers or dilated veins in the esophagus (esophageal varices), etc.;
  • you have active lesions in a cerebral artery leading to bleeding into the brain (acute hemorrhagic stroke);
  • you suffer from severe liver disease (severe hepatopathy);
  • you are already taking medicines that may be harmful to the bone marrow (myelotoxic medicines), which reduce the production of red and white blood cells (see section “Other medicines and Chiaro”);
  • you are pregnant or breastfeeding (see section “Pregnancy and breastfeeding”).

In some cases, treatment with ticlopidine has been associated with the occurrence of leukopenia or agranulocytosis, sometimes with irreversible outcomes. Therefore, your doctor will prescribe Chiaro only when it is considered irreplaceable by other medicines.
Chiaro must absolutely not be used for primary prevention in clinically healthy individuals.

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 your doctor will perform tests to assess liver function, especially during the first months of treatment with Chiaro;
  • you suffer from kidney problems (renal insufficiency). Your doctor will evaluate whether to reduce the dose of Chiaro and will instruct you to discontinue treatment if hematological or bleeding complications occur.

Inform your doctor immediately if you experience any of the following symptoms, as treatment with Chiaro must be discontinued:

  • signs and symptoms possibly related to neutropenia, i.e., reduced number of neutrophils in the blood, such as: fever, sore throat, oral ulcers;
  • signs and symptoms possibly related to thrombocytopenia, i.e., reduced number of platelets in the blood, and/or coagulation disorders (hemostasis), such as: prolonged or unexpected bleeding, presence of bruises on the body (ecchymoses), appearance of spots on the skin associated with bleeding (purpura), dark stools;
  • signs and symptoms possibly related to acute and severe disorders of small blood vessels, damaging 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 inadequate bone marrow response (hemolytic anemia), neurological symptoms similar to transient ischemic attack or stroke, kidney disorders, and fever. The onset of thrombotic thrombocytopenic purpura may be sudden, most likely within the first 8 weeks of starting Chiaro treatment, and carries a high risk of fatal outcome;
  • inflammation of the liver with destruction of cells and tissues and/or blockage of 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, or pale stools, inform your doctor immediately. Your doctor will instruct you to stop treatment with Chiaro and perform liver function tests;
  • diarrhea associated with inflammation of the colon (colitis), including colitis with increased number of lymphocytes in the colon lining (lymphocytic colitis). If this effect is severe and persistent, your doctor will instruct you to discontinue treatment with Chiaro.

Your doctor will assess whether or not to resume treatment with Chiaro based on clinical and laboratory test results.

During treatment with Chiaro, the following may occur:

  • occurrence of adverse effects, sometimes serious and fatal, of hematological and hemorrhagic nature, such as reduced granulocyte levels (agranulocytosis), reduced number of all blood cells (pancytopenia), and, rarely, development of a tumor affecting white blood cells (leukemia). These serious adverse effects may be due to:
    • inadequate medical monitoring, delayed diagnosis, and inappropriate management of adverse 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”). Therefore, it is essential that you strictly follow your doctor’s instructions;
  • a reduction beyond normal limits in the number of white blood cells and platelets. For this reason, your doctor will instruct you to undergo a complete blood count test, including differential white blood cell count and platelet count. These tests must be performed under medical supervision at the beginning of treatment with Chiaro and every 2 weeks during the first 3 months. Additionally, if you discontinue treatment with Chiaro for any reason within the first 3 months, your doctor will instruct you to repeat these tests 2 weeks after stopping treatment. If blood tests confirm abnormally low levels of neutrophils (a type of white blood cell) or platelets, your doctor will instruct you to discontinue Chiaro and will monitor your blood parameters until they return to normal;
  • an increased risk of bleeding; therefore, certain measures are necessary in case of surgical procedures:
    • for minor surgical procedures (e.g., tooth extraction), inform your doctor and dentist that you are taking Chiaro;
    • before a scheduled surgical procedure, your doctor will instruct you to stop taking Chiaro at least 10 days prior (except when antithrombotic activity is specifically required); after stopping treatment, medical staff will assess whether the effect on bleeding time persists before proceeding with surgery;
    • in case of emergency surgery, medical staff will evaluate the appropriate method to minimize bleeding risk and prolonged bleeding time;
  • increased levels of high-density (HDL-C), low-density (LDL-C), and very low-density (VLDL-C) lipoproteins and blood fats (triglycerides), typically appearing after 1–4 months of treatment;
  • diarrhea, generally mild and transient, occurring mostly during the first three months of treatment and usually resolving within 1–2 weeks without the need to discontinue Chiaro;
  • skin irritations and swellings (skin rashes), mostly observed during the first three months of treatment and resolving within a few days after stopping treatment.

Be cautious when using Chiaro if you are allergic to other medicines similar to ticlopidine (thienopyridines), such as clopidogrel and prasugrel, as cross-reactions may occur (see section 4). Taking these medicines may cause allergic reactions ranging from moderate to severe, such as skin irritation (rash), facial swelling, especially around the eyes and mouth (angioedema or Quincke’s edema), and changes in platelet and white blood cell levels in the blood (thrombocytopenia and neutropenia).
Patients who have shown allergy to one thienopyridine may have a higher risk of developing the same or another reaction to another thienopyridine. Cross-reactivity and signs of hypersensitivity should be monitored in patients with known allergy to thienopyridines.

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

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

  • medicines potentially harmful to the bone marrow (myelotoxic medicines), which reduce the production of red and white blood cells. Concomitant use 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;
    • salicylate derivatives (by extrapolation from acetylsalicylic acid). However, if you have had a stent implanted (a device used to repair blocked or damaged arteries), your doctor will instruct you to take Chiaro together with aspirin for about one month after implantation;
    • oral anticoagulants and heparins. If these medicines are necessary for you, your doctor will closely monitor your clinical and laboratory parameters;
    • theophylline, used for respiratory problems. Your doctor will prescribe blood tests to monitor plasma levels of theophylline;
    • digoxin, used for heart conditions, as concomitant use with Chiaro slightly reduces its blood levels;
    • phenobarbital and phenytoin, medicines used to treat epilepsy;
    • medicines eliminated through the liver, as concomitant use with Chiaro prolongs their presence in the body. In such cases, your doctor will adjust the dose of these medicines at the start and after discontinuation of concomitant administration;
    • antacids, as they reduce ticlopidine blood levels;
    • cimetidine, used to treat gastric ulcers, as it significantly increases ticlopidine blood levels;
    • cyclosporine, a medicine used to modulate the immune response and prevent transplant rejection, as very rare cases of reduced cyclosporine blood levels have been reported; your doctor will monitor cyclosporine blood levels;
  • 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 arms and legs.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

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

Driving and using machines
Chiaro may cause adverse effects that may affect your ability to drive or operate machinery, such as dizziness. Therefore, exercise caution when driving or operating 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 exactly as directed by 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 daily, taken during
meals.
Use in children and adolescents
Use in children and adolescents is not recommended due to lack of clinical experience.
If you take more Chiaro than you should
If you take/ingest 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.
Management in case of overdose of Chiaro
In case of ingestion/overdose of Chiaro, severe gastrointestinal intolerance may occur. In such cases, in hospital you may receive induced vomiting, gastric lavage, and appropriate supportive therapy.
If rapid correction of prolonged bleeding time is required, you may be given a platelet transfusion, which can reverse the effects of ticlopidine.
Chiaro is not removed by dialysis.
If you forget to take Chiaro
Do not take a double dose to make up for a forgotten dose.
If you stop treatment with Chiaro
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Stop treatment with Chiaro and consult your doctor immediately if you experience any of the following
during treatment:

  • liver disease with destruction of cells and tissues and/or blockage of the bile ducts (cytolytic and/or cholestatic hepatitis) and severe, persistent cholestatic jaundice (see section “Warnings and precautions”);
  • severe diarrhoea with colitis, including colitis with increased 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):

  • decrease in the level of neutrophils in the blood (neutropenia), even severe, and decrease in the level of granulocytes (agranulocytosis) (see section “Warnings and precautions”);
  • headache, dizziness;
  • diarrhoea and feeling of discomfort (nausea) (see section “Warnings and precautions”);
  • increase in liver enzymes, increase (isolated or not) in alkaline phosphatase and transaminases (increase of more than twice the upper normal limits);
  • skin rashes, mostly associated with spots and small lesions or urticarial reactions, often accompanied by itching, which may be generalized (see section “Warnings and precautions”);
  • increase in blood cholesterol and triglyceride levels (see section “Warnings and precautions”).

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

  • cases of isolated decrease in platelets (thrombocytopenia), exceptionally accompanied by a decrease in the number of red blood cells (haemolytic anaemia);
  • generalized infection of the body (sepsis) with organ and tissue damage, and septic shock, which may be fatal complications of agranulocytosis;
  • sensory disturbances (peripheral neuropathy);
  • haemorrhagic complications, especially bruising (ecchymoses) and nosebleeds (epistaxis), presence of blood in urine (haematuria) or conjunctival haemorrhage, bleeding during and following surgical procedures, which may be severe and sometimes fatal (see section “Warnings and precautions”);
  • lesions affecting the inner lining of the stomach and duodenum (gastroduodenal ulcer);
  • increased blood bilirubin levels;
  • skin irritation associated with peeling of the skin (exfoliative dermatitis).

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

  • reduction in the number of all blood cells (pancytopenia); marked reduction in the bone marrow tissue responsible for blood cell production (aplastic anaemia); thrombotic thrombocytopenic purpura (an acute blood disorder characterized by formation of platelet aggregates that block blood vessels, causing insufficient oxygen supply to tissues in various organs, severe reduction in circulating platelets, which are consumed in forming the aggregates, and anaemia (lack of circulating haemoglobin)); a type of cancer affecting white blood cells (leukaemia); increase in platelet count beyond normal limits (thrombocytosis) (see section “Warnings and precautions”);
  • sensation of discomfort in the ears perceived as ringing or buzzing (tinnitus);
  • bleeding in the brain caused by rupture of a blood vessel (intracerebral haemorrhage);
  • liver disease with destruction of cells and tissues and/or 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 allergic reactions, increase beyond normal limits of a subgroup of white blood cells (eosinophilia), severe acute allergic reaction (anaphylaxis), rapid swelling of the skin and subcutaneous tissues (Quincke's oedema), joint pain (arthralgia), inflammation of blood vessels (vasculitis), chronic inflammatory connective tissue disease (lupus-like syndrome), allergic pulmonary disorders (allergic pneumopathy), kidney disease due to immunological mechanisms (hypersensitivity nephropathy), sometimes leading to renal failure;
  • severe diarrhoea with colitis, including colitis with increased number of lymphocytes within the lining of the colon (lymphocytic colitis) (see section “Warnings and precautions”);
  • cases of fatal hepatitis and fulminant hepatitis;
  • inflammatory disease of blood vessels in the skin (erythema multiforme), severe disease of the skin and mucous membranes (Stevens-Johnson syndrome), severe skin disease with skin cell death (Lyell's syndrome);
  • fever.

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

  • cross-sensitivity hypersensitivity reactions between thienopyridines, such as clopidogrel and prasugrel (see section “Warnings and precautions”);
  • itching, red-coloured 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 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 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 Chiaro

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp". The expiry date refers to the last day of that month.
The stated expiry date applies to the product in its original, unopened packaging, correctly stored.
This medicine does not require any special storage conditions.
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. Package contents and other information

What Chiaro contains

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

Description of the appearance of Chiaro and package contents
Chiaro is available as film-coated tablets, packed in blisters.
Each package contains two blisters with 15 tablets each.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
NEOPHARMED GENTILI S.p.A.
Via San Giuseppe Cottolengo, 15
20143 Milan
Manufacturer
Fine Foods & Pharmaceuticals NTM S.p.A.
Via Grignano 43
24041 – Brembate (BG)