Tiklid

Patient Information Leaflet

Tiklid 250 mg film-coated tablets

ticlopidine 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, consult 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 side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Tiklid is and what it is used for

Tiklid contains the active substance ticlopidine, which belongs to the class of antiplatelet agents,
medicines that improve blood circulation by preventing the formation of blood clots (thrombi).
Tiklid is used:

• to prevent blockage of blood flow to the brain and heart (ischaemia) in people who have a high risk of blood clot formation (peripheral arterial disease, previous myocardial infarction and recurrent or non-recurrent ischaemia, ischaemic stroke, unstable angina);
• to prevent closure of heart bypass grafts (aortocoronary bypasses);
• during surgical procedures requiring artificial circulation (extracorporeal circulation);
• during haemodialysis sessions;
• if you suffer from central retinal vein thrombosis;
• in people who have had a heart attack or ischaemic attacks, only if they are intolerant to acetylsalicylic acid (ASA), or if treatment with acetylsalicylic acid has proven ineffective.

Due to its side effects, this medicine should only be used when it is indispensable and when it is not possible
to use another medicine different from Tiklid.

2. What you should know before taking Tiklid

Do not take Tiklid

• if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• if you have or have had abnormalities in blood cell levels (leukopenia, thrombocytopenia, and agranulocytosis);
• if you suffer from bleeding disorders (hemorrhagic diathesis), including prolonged bleeding;
• if you have lesions in the esophagus or stomach with a tendency to bleed (gastrointestinal ulcers, esophageal varices, etc.);
• if you suffer from cerebrovascular disorders (acute hemorrhagic stroke);
• if you have severe liver problems (severe hepatopathy);
• if you are taking other medicines that may interfere with bone marrow function (myelotoxic drugs);
• if you are pregnant or breastfeeding.

Do not use this medicine for primary prevention if you do not have any of the conditions listed in section 1.
Warnings and precautions
Talk to your doctor or pharmacist before taking Tiklid.
Adverse events, sometimes serious, of hematological and hemorrhagic nature may occur. Alterations in blood components such as reduced white blood cells (agranulocytosis), reduction of all blood cells (pancytopenia), and rare cases of leukemia have been reported after marketing authorization, sometimes with fatal outcome (see section 4).
Such serious events may be associated with:

• inadequate monitoring, delayed diagnosis, and inadequate treatment of side effects;
• concomitant administration of anticoagulants or antiplatelet agents such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). However, in the case of stent implantation, ticlopidine must be combined with aspirin (100–325 mg daily) for approximately one month after implantation.

It is essential to strictly follow the indications, precautions, and contraindications of ticlopidine.
Treatment must be carried out under close medical supervision, especially during the first three months, to monitor for possible side effects.
If you notice any of the following conditions, stop treatment immediately and inform your doctor:

• sore throat, fever, mouth sores (symptoms of neutropenia);
• bleeding, even prolonged, or bruising (hematomas), skin rash associated with bleeding (purpura), dark stools (symptoms of thrombocytopenia and/or coagulation disorders);
• skin rash associated with bleeding and reduced platelets (symptoms of thrombotic thrombocytopenic purpura);
• yellowing of the skin (jaundice), dark urine, pale stools (symptoms of hepatitis).

If thrombotic thrombocytopenic purpura is suspected, consult a specialist immediately, as there is a high risk of death. Onset may be sudden, and most cases have been reported within the first 8 weeks of starting therapy. Symptoms include reduced platelets (thrombocytopenia) and red blood cells (hemolytic anemia), neurological symptoms similar to transient ischemic attack (TIA) or stroke, kidney problems, and fever.
Resuming treatment with this medicine depends on your clinical condition and blood test results (hematological monitoring), which must be performed urgently.
Your doctor will prescribe blood tests at the beginning of treatment and then every 2 weeks for the first 3 months of therapy, and within 15 days of any interruption of Tiklid, if such interruption occurs within the first 3 months of treatment.
Your doctor will instruct you to discontinue treatment with this medicine if you develop low white blood cell count (neutropenia) or low platelet count (thrombocytopenia).
If you are scheduled for minor surgical procedures, such as tooth extraction, inform your doctor that you are taking this medicine.
Stop treatment at least 10 days before surgery to avoid the risk of bleeding.
In case of emergency surgery, inform your doctor about ongoing treatment so appropriate precautions can be taken to prevent bleeding risk.
This medicine should be used with caution if you are currently being treated with selective serotonin reuptake inhibitors (SSRIs).
Use this medicine cautiously if you are at risk of bleeding (hemorrhage) or have liver problems (hepatic dysfunction). Your doctor may recommend periodic liver function tests, especially during the first three months of treatment.
If you have kidney problems (renal insufficiency), consult your doctor, who may reduce the dose or discontinue treatment if bleeding or blood-related problems (hematopoietic disorders) occur.
Be cautious when using Tiklid 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 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 an increased risk of experiencing the same or another reaction to another thienopyridine. It is recommended to monitor for cross-reactivity and signs of hypersensitivity in patients with known allergy to thienopyridines.
Children and adolescents
The use of this medicine in children and adolescents is not recommended.
Other medicines and Tiklid
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Avoid using this medicine together with other medicines that may cause changes in blood cells (myelotoxic drugs).
Inform your doctor if you are taking the following medicines in addition to Tiklid, as they may increase the risk of bleeding:

• non-steroidal anti-inflammatory drugs (NSAIDs);
• antiplatelet agents, medicines used to increase blood fluidity;
• acetylsalicylic acid (except in cases of stent implantation, where combination is allowed) and its derivatives;
• oral and parenteral anticoagulants (heparin), medicines that improve circulation;
• pentoxifylline, a medicine used for poor blood circulation in arms and legs;
• a selective serotonin reuptake inhibitor (including, but not limited to, fluoxetine or fluvoxamine), medicines usually used to treat depression.

Inform your doctor and exercise particular caution if you are taking any of the following medicines, as specific precautions may be necessary:

• theophylline, a medicine used to treat asthma, as dosage adjustment may be required;
• digoxin, a medicine used to treat heart rhythm disorders;
• phenobarbital and phenytoin, medicines used to treat epilepsy;
• cimetidine and other medicines used to treat stomach disorders (antacids);
• cyclosporine, an immunosuppressant medicine used in transplant patients;
• ketamine, a medicine used in general anesthesia.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not use this medicine if you are pregnant or breastfeeding, except in cases of absolute necessity.
Driving and using machines
This medicine may cause dizziness and other side effects that could impair your ability to drive vehicles or operate machinery.

3. How to take Tiklid

Take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
For long-term treatment, the recommended dose is 1 or 2 tablets per day, taken during meals.
If you take more Tiklid than you should
If you accidentally take an excessive dose, contact your doctor immediately or go to the nearest hospital.
Overdose with this medicine may increase the risk of bleeding; if severe, treatment requires platelet transfusion.
In case of serious stomach or intestinal problems, treatment includes inducing vomiting, gastric lavage, and other supportive measures.
If you forget to take Tiklid
Do not take a double dose to make up for the missed tablet.
If you stop taking Tiklid
If you discontinue treatment with this medicine within the first three months, your doctor will instruct you to have a full blood test two weeks after stopping the therapy. Blood parameters must be monitored until they return to normal.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.
The use of this medicine may cause the following adverse effects:
Common (may affect up to 1 in 10 people)

• decrease in white blood cells, even severe (neutropenia, agranulocytosis);
• headache, dizziness;
• alteration of liver function (increase in liver enzymes, increase in alkaline phosphatase and transaminases);
• diarrhoea and nausea;
• skin irritations (maculopapular or urticarial rash), often accompanied by itching;
• increase in cholesterol and triglycerides.

Uncommon (may affect up to 1 in 100 people)

• decrease in platelets (thrombocytopenia), accompanied by a decrease in red blood cells (haemolytic anaemia);
• severe systemic infection (sepsis) and septic shock, which may occur as fatal complications of decreased white blood cells (agranulocytosis);
• sensory disturbances (peripheral neuropathy);
• haemorrhagic complications, especially bruising, presence of blood in urine (haematuria), or bleeding in the lower part of the eye (conjunctival haemorrhage), nosebleeds (epistaxis), bleeding during surgery (perioperative haemorrhage), and postoperative haemorrhages, which may be severe and sometimes fatal;
• development of lesions in the stomach and intestine (gastroduodenal ulcer);
• disturbances in liver function (increase in bilirubin);
• skin irritation associated with desquamation (exfoliative dermatitis).

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

• decrease in all blood cells (pancytopenia), severe reduction in bone marrow activity (bone marrow aplasia), blood disorders (thrombotic thrombocytopenic purpura, leukaemia, and thrombocytosis);
• perception of ringing or noise in the ear (tinnitus);
• brain haemorrhages (intracerebral);
• liver disorders, such as hepatitis (cytolytic and/or cholestatic hepatitis);
• yellowish discoloration of the skin due to liver dysfunction (cholestatic jaundice).

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

• immune system disorders, such as allergic manifestations, anaphylaxis (severe allergic reaction), facial swelling, especially around eyes and mouth (angioedema or Quincke's oedema), increase in white blood cells (eosinophilia), joint pain (arthralgia), inflammation of blood vessels (vasculitis), irritant skin disorders, joint pain and fever (lupus-like syndrome), lung disorders (allergic pneumonitis), kidney disorders (hypersensitivity nephropathy which may be associated with renal failure);
• severe diarrhoea associated with inflammation of the intestine (colitis and lymphocytic colitis). If this effect is severe, discontinue use of this medicine;
• fatal hepatitis and fulminant hepatitis;
• skin allergic reactions (erythema multiforme, Stevens-Johnson syndrome, and Lyell's syndrome);
• fever.

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

• cross-reactivity of hypersensitivity among 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 breathing difficulties (interstitial lung disease) caused by allergic pneumonia.

Reporting of adverse effects
If you experience any adverse effects, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report adverse effects directly via the Italian Medicines Agency (Agenzia Italiana del Farmaco) website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store Tiklid

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
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.
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 Tiklid contains

• The active substance is ticlopidine hydrochloride. Each tablet contains 250 mg of active substance.
• The other components are microcrystalline cellulose, povidone, anhydrous citric acid, maize starch, stearic acid, magnesium stearate, hypromellose, titanium dioxide, macrogol 8000.

Description of the appearance of Tiklid and contents of the pack
Pack containing 30 coated tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder
CHEPLAPHARM Arzneimittel GmbH, Ziegelhof 24, 17489 Greifswald, Germany

Manufacturers
SANOFI WINTHROP INDUSTRIE
1, rue de la Vierge
33440 Ambarès
France

SANOFI-AVENTIS S.A.
Carretera de la Batlloria a Hostalrich km 63.09
Riells
España

Sanofi S.p.A.
Viale Europa, 11
21040 Origgio (VA)
Italy

Sanofi S.r.l.
S.S. n. 17, km. 22
67019 Scoppito (AQ)
Italy

Farmea
Zac D’Orgemont
10 Rue Bouché Thomas
49000 Angers
France