Package leaflet: Information for the user

FLUPID 250 mg film-coated tablets

Ticlopidine hydrochloride
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What FLUPID is and what it is used for
What you need to know before taking FLUPID
How to take FLUPID
Possible side effects
How to store FLUPID
Contents of the pack and other information

1. WHAT FLUPID IS AND WHAT IT IS USED FOR

FLUPID contains the active substance ticlopidine, which belongs to the class of antiplatelet agents (medicines that inhibit platelet aggregation and prevent thrombus formation).
FLUPID is indicated:

For secondary prevention of occlusive ischemic events in the brain and cardiovascular system (events following blockage of blood flow in blood vessels of the brain and heart) in case of thrombotic risk (risk of developing blood clots that may obstruct blood vessels). Your risk of thrombosis is higher if:
You have peripheral obstructive arterial disease (a pathological condition characterized by obstruction of the arteries in the lower limbs).
You have had a myocardial infarction (an event caused by blockage of blood flow to the heart).
You have had recurrent transient ischemic attacks (temporary partial or complete reduction of blood supply to the brain) or ischemic stroke (sudden blockage of a blood vessel in the brain).
You have had unstable angina (chest pain caused by insufficient oxygen supply to the heart). Ticlopidine should be used after a previous myocardial infarction or transient ischemic attack only if you do not tolerate acetylsalicylic acid (ASA) or if ASA has proven ineffective.
For the prevention of re-occlusion of aortocoronary bypass grafts (new channels created to allow blood circulation from the aorta to the heart arteries, bypassing narrowings or blockages).
During extracorporeal circulation (a device that temporarily replaces heart and lung functions).
During hemodialysis (a physical therapy replacing kidney function).
For central retinal vein thrombosis (formation of clots in the central retinal vein, which drains blood from the retina of the eye).

2. WHAT YOU SHOULD KNOW BEFORE TAKING FLUPID

Do not take FLUPID

If you are allergic to the active substance (ticlopidine hydrochloride) or to any of the other ingredients of this medicine (listed in section 6).
If you currently have or have previously had leukopenia (reduced number of white blood cells in the blood), thrombocytopenia (reduced number of platelets in the blood), or agranulocytosis (reduced number of granulocytes in the blood).
If you have current or past hemorrhagic diathesis (tendency to bleed) or blood disorders (hemopathies) that prolong bleeding time.
If you have organic lesions prone to bleeding, such as gastrointestinal ulcers (lesions of the inner lining of the stomach or intestine), or esophageal varices (abnormal dilations of certain veins in the esophagus).
If you have acute hemorrhagic cerebrovascular accidents (sudden interruption of blood and oxygen flow to the brain due to bleeding).
If you have severe liver disease (hepatopathy).
If you are taking other medicines that may interfere with bone marrow function (myelotoxic medicines).
During pregnancy and breastfeeding (see “Pregnancy and breastfeeding”).

Do not take ticlopidine for primary prevention if you are clinically healthy.
The drug should only be used when absolutely necessary.
Warnings and precautions
Talk to your doctor or pharmacist before taking FLUPID.
Use of FLUPID may lead to adverse effects, sometimes serious and fatal (life-threatening), of hematological (blood-related) and hemorrhagic (bleeding-related) nature. Cases of agranulocytosis, pancytopenia (reduction in all types of blood cells), and rare cases of leukemia (blood cell cancer) have been reported (see section 4 “Possible side effects”).
These serious events may be associated with:

Inadequate monitoring, delayed diagnosis, and inappropriate therapeutic measures for adverse effects.
Concomitant administration of anticoagulants (medicines that reduce blood clotting) or antiplatelet agents such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). In the case of stent implantation (a device inserted to allow blood flow through arteries supplying the heart), ticlopidine must still 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 for ticlopidine.
Treatment must be carried out under close medical supervision, especially during the first three months, to monitor for possible adverse effects.
If you experience any of the following symptoms, stop treatment immediately and contact your doctor:

Sore throat, fever, mouth sores (symptoms of neutropenia);
Prolonged bleeding or bruising (hematomas), skin rash with bleeding (purpura), dark stools (symptoms of thrombocytopenia and/or coagulation disorders);
Skin rash with bleeding and low platelet count (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 treatment. Symptoms include low platelet count (thrombocytopenia) and low red blood cell count (hemolytic anemia), neurological symptoms similar to those of transient ischemic attack (TIA) or stroke, kidney dysfunction, 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 during the first 3 months of therapy, and within 15 days of any interruption of FLUPID, if such interruption occurs within the first 3 months of treatment. Your doctor will instruct you to stop treatment with this medicine if you develop low white blood cell count (neutropenia) or low platelet count (thrombocytopenia).
Use this medicine with caution if you are at risk of bleeding (hemorrhage) or if you 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 impairment), consult your doctor, who may reduce the dose or discontinue treatment if bleeding or blood disorders (hematopoietic disorders) occur.
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.
Children and adolescents
Use in children and adolescents is not recommended due to lack of clinical data (see “Do not take FLUPID”).
Other medicines and FLUPID
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Avoid taking FLUPID together with other medicines that may cause blood cell abnormalities (myelotoxic medicines).
Inform your doctor if you are taking the following medicines along with FLUPID, as they may increase the risk of bleeding (hemorrhage):

Non-steroidal anti-inflammatory drugs (NSAIDs);
Antiplatelet agents, medicines used to improve blood fluidity;
Acetylsalicylic acid (except in cases of stent implantation, where combination is allowed) and its derivatives;
Oral and parenteral anticoagulants (e.g., heparin), medicines that improve circulation.

Inform your doctor and be especially cautious 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.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not take ticlopidine during pregnancy.
Breastfeeding
Do not take ticlopidine while breastfeeding.
Driving and use of machines
Adverse effects of ticlopidine, such as dizziness, may impair your ability to drive or operate machinery; therefore, do not drive or exercise caution while being treated with FLUPID.
FLUPID 250 mg film-coated tablets contain lactose. If you have been diagnosed by your doctor with an intolerance to certain sugars, contact your doctor before taking this medicine.

3. HOW TO TAKE FLUPID

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 treatment is 1 or 2 tablets daily, taken during
meals.
If you take more FLUPID than you should
Taking an excessive dose of FLUPID may increase the risk of bleeding (haemorrhage).
Severe gastrointestinal intolerance (problems affecting the stomach and intestine) may occur. In such
cases, induction of vomiting, gastric lavage (emptying and washing out of the stomach), and other
general supportive measures are recommended.
Ticlopidine is not removed by dialysis.
If you forget to take FLUPID
Do not take a double dose to make up for the missed dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everybody experiences them.
The use of this medicine may cause the following adverse reactions:

Common (may affect up to 1 in 10 people)

Neutropenia, even severe, agranulocytosis.
Headache, dizziness.
Diarrhea and nausea.
Increase in liver enzymes, increase in alkaline phosphatase and transaminases (increase of more than twice the upper normal limits).
Skin rash, mostly maculopapular or urticarial, often accompanied by itching, which may also be generalized.
Increase in blood cholesterol and triglyceride (fats) levels.

Uncommon (may affect up to 1 in 100 people)

Thrombocytopenia, in rare cases accompanied by hemolytic anemia (decrease in hemoglobin level due to destruction of red blood cells).
Sepsis (generalized infection) and septic shock, which may be fatal complications of agranulocytosis.
Sensory disturbances (peripheral neuropathy).
Hemorrhagic complications, especially bruising or ecchymoses, epistaxis (nosebleeds), hematuria (blood in urine), conjunctival hemorrhage (bleeding in the eye), bleeding during and after surgery, which may be severe and sometimes fatal.
Gastroduodenal ulcer (lesion of the inner lining of the stomach and intestine).
Increased bilirubin levels.
Exfoliative dermatitis (skin inflammation).

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

Pancytopenia (decrease in all blood cells), aplastic anemia (marked reduction or absence of bone marrow tissue producing blood cells), thrombotic thrombocytopenic purpura, leukemia, and thrombocytosis.
Tinnitus (ringing in the ears).
Intracerebral hemorrhage (bleeding in the brain).
Hepatitis (cytolytic and/or cholestatic) and cholestatic jaundice.

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

Immunological reactions with various manifestations, for example allergic reactions, eosinophilia (elevated concentration of eosinophils, a type of white blood cells, in the blood), anaphylaxis (severe, rapidly developing allergic reaction), angioedema (sudden swelling of skin or mucous membranes), arthralgia (joint pain), vasculitis (inflammation of blood vessels), lupus-like syndrome (symptoms similar to systemic lupus erythematosus, a chronic autoimmune disease affecting often the heart, skin, lungs, vascular endothelium, liver, kidneys, and nervous system), allergic pneumonitis (allergic lung disease), nephropathy (kidney disorder) due to hypersensitivity, sometimes leading to renal failure.
Severe diarrhea with colitis (inflammation of the colon), including lymphocytic colitis.
Cases of fatal hepatitis and fulminant hepatitis.
Skin disorders such as erythema multiforme (inflammation of blood vessels associated with skin and mucosal lesions), Stevens-Johnson syndrome (a severe disease of the skin and mucous membranes often caused by an acute allergic reaction to drugs), and Lyell's syndrome (the most severe form of Stevens-Johnson syndrome, in which the epidermis detaches in sheets).
Fever.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, please contact your doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE FLUPID

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month and applies to the product in its original, unopened packaging stored under proper conditions.
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 you no longer use. This will help protect the environment.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What FLUPID contains
One coated tablet contains:
Active substance: ticlopidine hydrochloride 250 mg.
Other components: lactose; hydroxypropylcellulose; microcrystalline cellulose; talc; magnesium stearate;
sodium croscarmellose; macrogol 6000; titanium dioxide.

Description of the appearance of FLUPID and contents of the package
Coated, round, almost white tablets.
Carton box containing 2 blisters with 15 coated tablets each.

Marketing Authorization Holder
FARMACEUTICI DAMOR S.p.A. - Via E. Scaglione, 27 - 80145 Naples.

Manufacturer

Fine Foods & Pharmaceuticals N.T.M. S.p.A., Via Grignano, 43 - 24041 Brembate (BG): manufacturing, quality control and batch release.
Farmaceutici Damor S.p.A. - Via E. Scaglione, 27 - 80145 Naples: batch release.