Ifapidin

Package leaflet: Information for the user

IFAPIDIN
250 mg, coated tablets
Ticlopidini hydrochloridum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents

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

1. What Ifapidin is and what it is used for

The active substance in Ifapidin, ticlopidine, inhibits platelet aggregation and the release of substances involved in blood coagulation, thus preventing the formation of arterial and venous thrombi. The mechanism of action of ticlopidine involves inhibition of ADP-dependent binding of fibrinogen to the glycoprotein (IIb and IIIa) receptor on the platelet surface. Ticlopidine reduces fibrinogen concentration, prolongs bleeding time, and decreases blood viscosity. After oral administration, it is rapidly and almost completely absorbed from the gastrointestinal tract. Anti-aggregatory effects are detectable after 48 hours, reaching maximum after 5–8 days. After discontinuation of the drug, bleeding time and other platelet function test results return to normal within about one week. Ticlopidine is mainly metabolized in the liver and excreted in urine (50%–60% of the administered dose) and in faeces (20%–30% of the administered dose).

Ticlopidine, as a selective inhibitor of platelet aggregation, is used in the treatment of vascular disorders and for the prevention of their complications:

• Prevention of ischemic strokes and transient ischemic attacks (TIAs),
• Prevention of re-occlusion after myocardial infarction and prevention of recurrent infarctions,
• Prevention of peripheral vascular thrombosis in peripheral arterial disease,
• Prevention of secondary atherosclerotic and diabetic angiopathy.

Additionally, in surgery, both before and after procedures involving extracorporeal circulation, and during hemodialysis, it improves dialysis efficacy, protects platelets, and reduces the amount of heparin required. It is also used therapeutically and preventively in platelet disorders.

2. Important information before taking Ifapidin

When not to take Ifapidin

• If you are allergic to ticlopidine or to any of the other ingredients of this medicine (listed in section 6).
• If you have a tendency to bleed (e.g. hemophilia).
• If you have other diseases associated with bleeding or predisposition to bleeding, such as active peptic ulcer of the stomach or duodenum or the acute phase of hemorrhagic stroke.
• If you have a blood-forming disorder or a coagulation disorder associated with prolonged bleeding time.
• If you have severe hepatic insufficiency.
• If you have previously experienced diseases associated with reduced white blood cell or platelet counts.
• If you currently have reduced numbers of certain white blood cells (neutropenia) or platelets (thrombocytopenia).
• For primary prevention of thrombosis in healthy individuals.

Warnings and precautions

Before starting treatment with Ifapidin, discuss this with your doctor or pharmacist.

• Always take Ifapidin exactly as prescribed by your doctor.
• If you have previously experienced allergic (hypersensitivity) reactions to another thienopyridine (such as clopidogrel or prasugrel; ticlopidine also belongs to this class), inform your doctor before starting treatment with Ifapidin. Patients who have previously experienced mild to severe allergic reactions (such as rash or angioedema [swelling of the face or throat]) and/or hematological reactions (thrombocytopenia and neutropenia) to one thienopyridine may be at increased risk of developing the same or another reaction to another thienopyridine.
• Inform your doctor about all previous and current medical conditions, both before and during treatment with Ifapidin.
• Special caution is required when using Ifapidin in patients with impaired liver function; therefore, always inform your doctor if you have liver disease.
• The use of this medicine increases the risk of bleeding. Therefore, before any planned or emergency surgical or dental procedure involving a risk of bleeding, inform your doctor or dentist that you are taking Ifapidin.
• Laboratory tests should be performed regularly at intervals determined by your doctor, both before and during treatment (especially during the first 3 months).
• If persistent or severe diarrhea or nausea occurs during treatment, discontinue the medicine and consult your doctor.
• Immediately contact your doctor if any of the following symptoms occur: signs of skin allergy (e.g. urticaria, swelling of hands, eyelids, throat, or external genitalia [Quincke's edema]), fever, sore throat, oral mucosal ulcers, petechial hemorrhagic spots on the skin or bleeding from mucous membranes, bruising, symptoms of transient ischemic attack (numbness, speech difficulties, weakness on one side of the body, drooping of the mouth corner, double vision, dizziness, balance disturbances), stroke, confusion, prolonged or unusual bleeding, dark stools, extreme fatigue, pallor, jaundice, dark urine, or pale stools.

Children and adolescents

Due to lack of experience, the use of Ifapidin is not recommended in children and adolescents.

Ifapidin and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

Due to an increased risk of bleeding, concomitant use of Ifapidin with the following medicines requires special caution and careful regular monitoring as advised by your doctor:

• Non-steroidal anti-inflammatory drugs (commonly prescribed for musculoskeletal disorders, inflammation, fever, and pain),
• Other antiplatelet agents,
• Various anticoagulant drugs (e.g. acenocoumarol) and heparins,
• Salicylic acid derivatives (acetylsalicylic acid, present in many medicines used to relieve pain and fever and to prevent blood clotting),
• Selective serotonin reuptake inhibitors (including, but not limited to, fluoxetine or fluvoxamine), commonly used in the treatment of depression,
• Pentoxifylline, a drug used in the treatment of circulatory disorders in the hands and feet.

Concomitant use of Ifapidin with the following medicines should be avoided, or special caution and careful regular monitoring as advised by your doctor is required:

• Theophylline (commonly prescribed for breathlessness),
• Digoxin (commonly prescribed for heart failure and/or irregular heartbeat),
• Cyclosporine (used after organ transplantation to prevent rejection of the transplanted organ),
• Phenytoin (used in the treatment of seizures or facial pain).

Concomitant use of Ifapidin with the following medicines requires special caution:

• Antacids,
• Cimetidine (an anti-ulcer drug that works by reducing stomach acid production).

Taking Ifapidin with food

Ifapidin should be taken with food.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before taking this medicine.

Ifapidin is not recommended during pregnancy and breastfeeding, except when your doctor considers it absolutely necessary.

Breastfeeding

If treatment with Ifapidin is necessary during breastfeeding, breastfeeding should be discontinued.

Fertility

No impairment of fertility has been observed.

Driving and using machines

Very rarely, this medicine may cause dizziness, tinnitus, and may impair concentration. If you notice any of these symptoms, do not drive or operate machinery and avoid activities associated with a high risk of accidents. You should consult your doctor. Recommendations regarding restrictions or prohibition of driving and performing high-risk activities should be determined individually by the doctor for each patient.

3. How to use Ifapidin

This medicine should always be taken exactly as recommended by your doctor or pharmacist. If you have any doubts,
you should consult your doctor or pharmacist.
Adults
The recommended dose is 1 tablet twice daily. The medicine should be taken with food.
Elderly patients (over 65 years of age)
Ifapidin may be used at the standard adult dose.
Use in children
The use of Ifapidin is not recommended in children due to insufficient data on safety and efficacy.
Hepatic impairment
Special caution is required when administering Ifapidin to patients with liver dysfunction. In case of jaundice, dark urine, or pale stools (symptoms which may indicate hepatitis), the medicine should be discontinued immediately and your doctor should be notified (see also "Possible side effects").
Taking more Ifapidin than recommended
Overdosing on Ifapidin may be dangerous; therefore, if you have taken more tablets than recommended, you should contact your doctor immediately or go to the nearest hospital emergency department. Overdose may cause gastrointestinal symptoms. Overdosing may also increase the risk of bleeding.
Missing a dose of Ifapidin
If you miss a dose at the usual time, you should try to take it as soon as possible. However, if it is almost time for your next dose, do not take a double dose to make up for the missed tablet.
Stopping Ifapidin treatment
Do not stop taking this medicine arbitrarily or prematurely (except when severe adverse reactions occur), as this may lead to recurrence of the disease.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should contact your doctor immediately if any of the following symptoms occur:
Bleeding, fever, infection

Common (may occur in up to 1 in 10 patients)

• headache, dizziness, fever, sore throat, oral mucosal ulcers (neutropenia).

Uncommon (may occur in up to 1 in 100 patients)

• bleeding into the skin and mucous membranes (small red spots (petechiae) on the skin and mucous membranes, purpura (thrombocytopenia))
• bruising, nosebleeds, unusual bleeding, bleeding into the eyes, bleeding which may occur during or after surgical procedures (fatal outcomes have sometimes been observed)
• high fever, infectious ulcers of the mouth, throat, skin, or anal area (agranulocytosis). Sepsis and septic shock may occur – symptoms include high fever, chills, sudden drop in blood pressure (sepsis and septic shock may be life-threatening complications of agranulocytosis).

Rare (may occur in up to 1 in 1,000 patients)

• fever, petechiae (small red spots), with or without such symptoms as unexplained weakness, pallor, transient ischemic attack symptoms (numbness, speech difficulties, weakness on one side of the body, double vision, balance disturbances, etc.), stroke symptoms, yellowing of the skin or eyes (jaundice) (thrombotic thrombocytopenic purpura; TTP).

Allergic reactions:
Very rare (may occur in up to 1 in 10,000 patients)

• urticaria, difficulty breathing, nausea, dizziness, weakness (anaphylaxis),
• marked swelling of hands, eyelids, throat, and genital area (Quincke's edema), allergic pneumopathy (allergic interstitial lung disease), allergic nephritis, sometimes leading to renal failure.

Other adverse reactions
Very rare (may occur in up to 1 in 10,000 patients)
During treatment with ticlopidine, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported, initially presenting as red, target-like lesions or round spots, often with centrally located blisters, mainly on the trunk. Additional symptoms to watch for include: ulcers of the mouth, throat, nose, genital organs, and conjunctivitis (red, swollen eyes). Skin lesions are often accompanied by influenza-like symptoms. The rash may worsen, progressing to generalized skin blistering or skin peeling.
Persistent and/or severe diarrhea (severe diarrhea with colitis), nausea.
Signs of hepatitis/liver failure: jaundice, dark urine, pale stools.

Uncommon (may occur in up to 1 in 100 patients)
Severe skin inflammation with skin peeling and blister formation (exfoliative dermatitis).
Peptic ulcer disease of the stomach and duodenum: burning pain in the upper abdomen, most intense when fasting, which may be temporarily relieved by food. Complications such as gastrointestinal bleeding or perforation of the stomach or intestines may occur.
If any of these symptoms occur, treatment with the medicine should be stopped immediately.

List of adverse reactions (and frequency of occurrence):
Common (may occur in up to 1 in 10 patients)

• During treatment with Ifapidin, changes in laboratory test results may occur. Decreased white blood cell count may occur, very rarely in severe form. Severe symptoms, mucosal ulcers, fever, sore throat associated with decreased white blood cell count (agranulocytosis) occurred mainly during the first 3 months of treatment.
• dizziness, headache
• diarrhea and nausea
• increased liver enzyme activity (increased alkaline phosphatase and transaminase levels)
• skin rash (often with itching). Skin symptoms may spread over the entire body surface.
• increased serum cholesterol and triglyceride levels (fatty substances in the blood).

Uncommon (may occur in up to 1 in 100 patients)

• decreased platelet count (sometimes associated with anemia due to red blood cell destruction)
• sepsis and septic shock may be life-threatening complications of agranulocytosis (see section "Bleeding, fever, infection")
• bleeding (see section "Bleeding, fever, infection")
• unusual sensations, numbness and tingling of limbs (peripheral neuropathy)
• gastric and duodenal ulcer (see section "Other adverse reactions")
• increased blood bilirubin levels
• exfoliative dermatitis (see section "Other adverse reactions").

Rare (may occur in up to 1 in 1,000 patients)

• decreased red blood cell, white blood cell, and platelet counts, bone marrow failure, leukemia, increased platelet count
• tinnitus
• intracranial hemorrhage
• hepatitis.

Very rare (may occur in up to 1 in 10,000 patients)

• immunological reactions with various symptoms: anaphylactic reaction, Quincke's edema, allergic interstitial lung disease, allergic nephritis, joint pain, vasculitis, lupus-like syndrome, allergic neuritis, and increased eosinophilia (a type of white blood cells)
• severe diarrhea with colitis (see section "Other adverse reactions")
• hepatitis with fatal outcome (see section "Other adverse reactions")
• (erythema multiforme), Stevens-Johnson syndrome, exfoliative dermatitis (see section "Other adverse reactions")
• fever.

Frequency not known (cannot be estimated from available data)

• cross-hypersensitivity reactions among thienopyridines (e.g., clopidogrel, prasugrel)

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Ifapidin

Store below 25 °C.
Keep the medicine in a place out of sight and out of reach of children.

6. Contents of the packaging and other information

What Ifapidin contains
The active substance is ticlopidine hydrochloride. Each coated tablet contains 250 mg of
ticlopidine hydrochloride.
The other ingredients are: microcrystalline cellulose, potato starch, citric acid monohydrate, stearic acid, colloidal anhydrous silica, magnesium stearate, hypromellose,
macrogol 6000, titanium dioxide (E 171).

What Ifapidin looks like and contents of the pack
Appearance of the tablets: white or almost white, round, biconvex coated tablets with the letter "E" and the number "421" engraved on one side.
Pack sizes:
20 coated tablets (2 blisters of 10 tablets or 1 blister of 20 tablets) and
60 coated tablets (6 blisters of 10 tablets or 3 blisters of 20 tablets).
Aluminium/PVC blisters in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
EGIS Pharmaceuticals PLC
Kereszturi út 30-38
1106 Budapest
Hungary

Manufacturer
EGIS Pharmaceuticals PLC
Bökényföldi út 118-120
1165 Budapest
Hungary

For further information, please contact the local representative of the Marketing Authorisation Holder.
EGIS Polska Sp. z o.o.
ul. Komitetu Obrony Robotników 45D
02-146 Warsaw
Tel.: +48 22 417 92 00