Clox

Package leaflet: Information for the patient

CLOX 250 mg 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, 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 could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What CLOX is and what it is used for

CLOX contains ticlopidine, an active substance belonging to a group of medicines called
antiplatelet agents. Platelets are blood components that clump together during blood
coagulation; by preventing this aggregation, antiplatelet drugs help prevent the
formation of blood clots (thrombi).
CLOX is used:

• for secondary prevention of blocked blood flow to the brain and heart (ischaemia) in patients who have a high risk of blood clot formation in blood vessels (thrombi), for example if:
• you have had a stroke;
• you have previously had a mini-stroke (TIA) or a heart attack and treatment with acetylsalicylic acid (ASA), commonly known as aspirin, has not been effective or is not possible because you are intolerant to acetylsalicylic acid;
• you have blockage of the arteries in the legs (peripheral arterial occlusive disease);
• you suffer from unstable angina, a condition characterised by chest pain occurring even at rest;
• to prevent closure of blood vessels that have undergone bypass surgery (a procedure performed to restore blood flow in a blocked vessel);
• during heart surgeries requiring a stopped heart and artificial circulation (extracorporeal circulation);
• in case of blood clot formation (thrombi) in the eye (central retinal vein);
• in patients undergoing blood purification through an artificial kidney (haemodialysis).

2. What you should know before taking CLOX

Do not take CLOX if:

• you are allergic (hypersensitive) to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• you are experiencing bleeding from a blood vessel in the brain (acute hemorrhagic stroke);
• you have a tendency to bleed (hemorrhagic diathesis), for example, blood disorders causing coagulation problems;
• you have any medical condition that increases your risk of internal bleeding, such as a stomach or intestinal ulcer, or esophageal varices;
• you have or have had a reduction in blood cells: white blood cells (leucopenia), granulocytes (agranulocytosis), or platelets (thrombocytopenia);
• you are taking medicines that affect the bone marrow (myelotoxic) and that could cause a reduction in blood cells (see "Other medicines and CLOX");
• you have severe liver problems;
• you are pregnant or breastfeeding, unless otherwise directed by your doctor (see "Pregnancy and breastfeeding").

Do not use this medicine for primary thrombosis prevention, i.e., if you do not have any of the conditions listed in section 1.

Warnings and precautions

Talk to your doctor or pharmacist before taking CLOX.

Use this medicine with caution if:

• you are at risk of bleeding (haemorrhage);
• you suffer from kidney problems (renal failure); in this case, your doctor may reduce your dose;
• you have liver problems, as you may be more likely to experience liver-related adverse effects, including cases of hepatitis (liver inflammation), especially during the first months of treatment. Be alert: if during treatment with CLOX you notice signs of hepatitis, such as yellowing of the skin or eyes (jaundice), dark urine, or pale stools, STOP TAKING CLOX AND CONTACT YOUR DOCTOR IMMEDIATELY (see section 4 – "Possible side effects").

Risk of bleeding

CLOX increases the risk of bleeding (haemorrhage).

Inform your doctor if:

• you are taking other medicines that affect blood coagulation, such as: blood-thinning medicines (oral anticoagulants or injectable ones like heparin), or medicines used for pain and inflammation (acetylsalicylic acid or NSAIDs) (see section “Other medicines and CLOX”);
• you are scheduled for minor surgery, such as tooth extraction;
• you are scheduled for surgery, as CLOX therapy should be discontinued at least ten days before the procedure;
• you require emergency surgery, so that appropriate precautions can be taken to avoid the risk of bleeding.

Blood-related adverse effects

CLOX increases the risk of blood-related adverse effects, especially during the first 3 months of treatment. If during treatment with CLOX you notice:

• fever, sore throat, mouth ulcers, general malaise and widespread pain, possible signs of infection due to reduced neutrophils or granulocytes in the blood;
• prolonged or unexpected bleeding, red spots on the skin of varying size from small dots to extensive bruises (ecchymoses, purpura), dark stools, possible signs of reduced platelets;
• fever, bleeding or bruising, fatigue, confusion, headache, weakness in arms or legs, altered consciousness or vision, possible signs of thrombotic thrombocytopenic purpura (a condition that may be fatal);

IN ALL THESE CASES, STOP TAKING CLOX AND CONTACT YOUR DOCTOR IMMEDIATELY (see section 4 – "Possible side effects").

Blood tests

Your doctor will prescribe certain blood tests at the beginning of CLOX treatment and then every two weeks during the first three months of therapy, to monitor for possible changes in blood parameters. If test results are abnormal, your doctor will assess whether your treatment needs to be adjusted. Your doctor will instruct you to discontinue treatment with this medicine if you develop a reduction in white blood cells (neutropenia) or a reduction in platelets (thrombocytopenia).

Your doctor will also prescribe a complete blood count after stopping CLOX treatment. If necessary, you may be asked to repeat the test until blood parameters return to normal levels.

Children and adolescents

The use of CLOX is not recommended in children and adolescents.

Other medicines and CLOX

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, as some drugs may interact with each other or increase the risk of even serious adverse effects.

Do not take CLOX if you are taking medicines that affect the bone marrow (myelotoxic) and that could cause a reduction in blood cells (see "Do not take CLOX").

Inform your doctor if you are taking:

• medicines that increase blood fluidity (antiplatelet agents) (see "Risk of bleeding");
• oral or parenteral anticoagulants (such as heparin) that improve blood circulation (see "Risk of bleeding");
• medicines used for pain and inflammation, NSAIDs such as acetylsalicylic acid or salicylate derivatives (except in cases of stent implantation, where combination is allowed) (see "Risk of bleeding");
• theophylline, a medicine used in respiratory diseases such as asthma;
• phenobarbital and phenytoin, medicines used to treat certain forms of epilepsy;
• digoxin, a medicine used to treat heart rhythm disorders;
• antacids or cimetidine, medicines used to treat stomach disorders, such as ulcers;
• cyclosporine, a medicine that suppresses the body's immune defenses and is used in transplants or autoimmune diseases;
• 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

CLOX should not be used during pregnancy and breastfeeding, except in cases of absolute necessity.

If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.

Driving and using machines

CLOX may cause dizziness. Be cautious before driving vehicles or operating machinery.

3. How to take CLOX

Take this medicine exactly as your doctor has told you. If you are not sure, consult your doctor or pharmacist.
For long-term treatment, the recommended dose is 1 or 2 tablets daily, taken orally (by mouth) during meals.
If you take more CLOX than you should, you may experience unwanted effects on the stomach or intestine; furthermore, the risk of bleeding (haemorrhage) is increased.
If you accidentally take too much CLOX, contact your doctor immediately or go to the nearest hospital, as appropriate measures will be necessary.
If you forget to take CLOX
Do not take a double dose to make up for the forgotten dose. Consult your doctor for advice on what to do.
If you stop taking CLOX
It is important that you take this medicine regularly. Do not stop treatment without consulting your doctor.
If you have any doubts about how to use this medicine, speak to your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
STOP TAKING CLOX AND CONTACT YOUR DOCTOR IMMEDIATELY if you experience any of the following:

• severe allergic reactions, such as swelling (angioedema) of the face, eyes, lips, throat, difficulty breathing and chest tightness (allergic pneumonitis), changes in heart rhythm possibly leading to a sudden drop in blood pressure (anaphylactic shock). These reactions are very rare;
• severe blood infection (sepsis) presenting with fever, rapid breathing, increased heart rate, confusion and sudden drop in blood pressure (septic shock). These reactions are uncommon side effects.

The use of this medicine may cause the following side effects:
Common side effects (may affect up to 1 in 10 people)

• decrease in neutrophils or granulocytes in the blood, manifesting as fever, sore throat, mouth ulcers, general malaise and widespread pain. If this occurs, stop taking CLOX and consult your doctor immediately (see section 2 - “Side effects affecting the blood”);
• more or less sudden appearance of skin lesions, such as discoloured spots or widespread rash (maculopapular or urticarial rash), possibly accompanied by itching;
• headache, dizziness;
• diarrhoea, nausea;
• increased levels of cholesterol (hypercholesterolaemia), triglycerides (hypertriglyceridaemia), or liver enzymes (such as alkaline phosphatase and transaminases) in the blood.

Uncommon side effects (may affect up to 1 in 100 people)

• decrease in platelets (thrombocytopenia), manifesting as prolonged or unexpected bleeding, red spots on the skin of varying size from pinpoint to large bruises (ecchymoses, purpura), dark stools. In rare cases, destruction of red blood cells may also occur, leading to a reduced red blood cell count (haemolytic anaemia). If this occurs, stop taking CLOX and consult your doctor immediately (see section 2 - “Side effects affecting the blood”);
• bleeding, bruising and red spots (ecchymoses) on the skin, nosebleeds (epistaxis) or conjunctival bleeding, blood in the urine (haematuria), bleeding during or after surgery, which may be severe and sometimes fatal. If this occurs, stop taking CLOX and consult your doctor immediately (see section 2 - “Side effects affecting the blood”);
• severe systemic infection (sepsis) and septic shock, which may occur as fatal complications of low white blood cell count (agranulocytosis);
• altered sensation (peripheral neuropathy);
• stomach or duodenal ulcer;
• increased bilirubin levels in the blood;
• skin inflammation and peeling.

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

• thrombotic thrombocytopenic purpura, presenting as fever, bleeding or bruising, fatigue, confusion, headache, weakness in arms or legs, changes in consciousness or vision. If this occurs, stop taking CLOX and consult your doctor immediately (see section 2 - “Side effects affecting the blood”);
• yellowing of the skin or eyes (jaundice), dark urine and pale stools (possible signs of hepatitis). If this occurs, stop taking CLOX and consult your doctor immediately (see section 2 - “Warnings and precautions”);
• decrease in all blood cells (pancytopenia), due also to bone marrow problems (bone marrow aplasia), leukaemia (a blood cancer), increased platelet count in the blood (thrombocytosis);
• perception of ringing or buzzing sounds in the ears (tinnitus);
• bleeding in the brain (cerebral haemorrhage).

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

• immune system disorders, such as allergic manifestations, anaphylaxis (severe allergic reaction), facial swelling especially around the eyes and mouth (angioedema or Quincke's oedema), increased 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 kidney failure);
• severe skin rashes with redness, peeling and/or blistering (e.g. erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome);
• severe diarrhoea with inflammation of the intestine (colitis). If this effect is severe, discontinue taking this medicine;
• very severe (fulminant) hepatitis, potentially fatal;
• immune system disorders, such as allergic manifestations, anaphylaxis (severe allergic reaction), facial swelling especially around the eyes and mouth (angioedema or Quincke's oedema);
• fever.

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 the website: “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 CLOX

Keep this medicine out of the sight and reach of children.
Store this medicine at room temperature, away from intense and direct light.
Do not use this medicine after the expiry date stated on the packaging. 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 CLOX contains
The active substance is: ticlopidine hydrochloride.
One tablet contains: 250 mg of ticlopidine hydrochloride.
The other components are: microcrystalline cellulose, starch, methylcellulose, precipitated silica,
magnesium stearate, titanium dioxide (E171), gum arabic.
Description of the appearance of CLOX and pack contents
CLOX is available in packs of 30 tablets.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
I.B.N. Savio S.r.l. - Via del Mare, 36 - Pomezia (RM)
Manufacturer
Special Product’s Line S.p.A. - Strada Paduni, 240 – Anagni (FR)