Patient Information Leaflet

AGAPURIN, 100 mg, coated tablets
Pentoxifylline
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.
Keep this leaflet as you may need to read it again.
If you have any further questions, please consult 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 similar.
If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.
Contents of the leaflet

What Agapurin is and what it is used for
Important information before taking Agapurin
How to take Agapurin
Possible side effects
How to store Agapurin
Contents of the pack and other information

1. What Agapurin is and what it is used for

The active substance in Agapurin is pentoxifylline. The medicine improves blood circulation by
increasing the flexibility of red blood cells, inhibiting blood coagulation and reducing blood viscosity, and by suppressing inflammatory activity of white blood cells.
Indications:

Peripheral arterial and arterio-venous circulatory disorders caused by atherosclerosis, diabetes, inflammatory or functional conditions; intermittent claudication or rest pain, diabetic angiopathy, obliterative vascular disease, trophic changes (post-thrombotic syndrome, leg ulcers, gangrene), angioneuropathies;
Circulatory disorders in the eyeball (acute and chronic circulatory disturbances in the retina and choroid);
Inner ear function disorders (hearing disturbances, sudden hearing loss, etc.) caused by circulatory disorders;
Cerebral ischemia (conditions following stroke, cerebrovascular disorders with symptoms such as lack of concentration, dizziness, memory disturbances, etc.).

Agapurin is intended for use in adult patients.

2. Important information before using Agapurin

When not to use Agapurin
if the patient is allergic to pentoxifylline, other methylxanthines, or to any of the other
components of this medicine (listed in section 6);
if the patient has recently suffered a myocardial infarction or stroke;
if the patient has significantly increased bleeding or diseases with a high risk of
haemorrhage;
if the patient has experienced a retinal haemorrhage.
If any of the above situations occur, the patient should contact a doctor.

Warnings and precautions
Before starting treatment with Agapurin, discuss this with a doctor or pharmacist.
The doctor should consider the benefit-risk ratio of using Agapurin in patients with
hypotension, severe cardiac arrhythmias, advanced atherosclerosis of coronary and cerebral vessels,
acute myocardial infarction, diabetes, or severe renal impairment.
If symptoms of anaphylactic or pseudoanaphylactic reactions occur, treatment with Agapurin must be discontinued immediately and the patient should contact their doctor without delay.
Patients with severe cardiac arrhythmias, advanced atherosclerosis of coronary and cerebral vessels, hypotension, or history of myocardial infarction should be under continuous medical supervision during treatment with Agapurin.
Renal impairment (creatinine clearance below 30 ml/min) and severe hepatic dysfunction may delay the elimination of pentoxifylline. In such cases, the dose should be reduced and the patient should remain under continuous medical supervision.
Patients with an increased tendency to bleed who are taking Agapurin concomitantly with vitamin K antagonists, antiplatelet agents, or antidiabetic drugs should be under continuous medical supervision.
Patients taking Agapurin together with antidiabetic drugs should be under continuous medical supervision (see "Agapurin with other medicines", below).
In patients with low blood pressure or heart disease, administration of Agapurin may lead to a sudden drop in arterial blood pressure and, rarely, back pain or retrosternal pain. Therefore, blood pressure should be monitored during treatment.
Patients taking Agapurin concomitantly with ciprofloxacin should be under continuous medical supervision (see "Agapurin with other medicines", below).
Patients taking pentoxifylline concomitantly with theophylline should be under continuous medical supervision (see "Agapurin with other medicines").

Agapurin with other medicines
Inform your doctor or pharmacist about all medicines currently taken, recently taken, or planned for use.
Agapurin may enhance the effects of antihypertensive drugs (including angiotensin-converting enzyme inhibitors) or other drugs that lower arterial blood pressure (e.g. nitrates).
In patients treated with insulin or oral antidiabetic drugs, administration of high doses of Agapurin may intensify the reduction in blood glucose concentration. Therefore, diabetic patients should be under continuous medical supervision.
In patients taking pentoxifylline concomitantly with vitamin K antagonists, increased anticoagulant effect has been reported. When initiating or adjusting the dose of Agapurin in these patients, close monitoring of anticoagulant activity is recommended.
Due to increased risk of bleeding, caution is advised in patients taking pentoxifylline concomitantly with antiplatelet agents such as: clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, non-selective nonsteroidal anti-inflammatory drugs (other than selective COX-2 inhibitors), acetylsalicylates (acetylsalicylic acid or lysine acetylsalicylate), ticlopidine, dipyridamole.
In some patients, concomitant use of pentoxifylline and theophylline may increase plasma theophylline concentrations and intensify adverse effects associated with its use.
In some patients, concomitant use of pentoxifylline and ciprofloxacin may increase serum concentrations of pentoxifylline. Therefore, increased frequency and severity of adverse reactions associated with concomitant use of these two active substances may occur.
Concomitant use of Agapurin with cimetidine may increase plasma concentrations of pentoxifylline and its active metabolite.

Agapurin with food and drink
See section 3.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Use of this medicine is not recommended in pregnant women or women who are breastfeeding.
In women who are breastfeeding, the doctor will decide whether potential benefits outweigh the risks to the infant.

Driving and operating machinery
This medicine has no influence on the ability to drive or operate machinery.

Agapurin contains 91.94 mg of monohydrate lactose and 97.168 mg of sucrose in each tablet
If the patient has previously been diagnosed with intolerance to certain sugars, they should consult a doctor before taking this medicine.

Agapurin contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, meaning the medicine is considered "sodium-free".

3. How to use Agapurin

This medicine should always be used according to the doctor's instructions. If in doubt, consult
your doctor or pharmacist.
The dosage is always determined by the doctor.
Adults
The recommended initial dose for use during the first week of treatment is 200 mg (2 tablets) three
times daily. If a significant drop in blood pressure or adverse effects affecting the gastrointestinal
tract or central nervous system occur, the doctor will decide whether to reduce the dose to 100 mg
(1 tablet) three times daily. For long-term treatment, the dose of 100 mg (1 tablet) three times
daily should be used.
Use in children and adolescents
There is limited experience with the use of this medicine in children and adolescents under
18 years of age. Therefore, the use of Agapurin is not recommended in this age group.
Dosing in patients with renal impairment
In patients with renal impairment (creatinine clearance < 30 ml/min), the dose should be reduced
to 50–70% of the usual recommended dose, depending on individual tolerance to treatment.
Dosing in patients with hepatic impairment
In patients with severe hepatic impairment, dose reduction is necessary. The treating physician
decides on the appropriate dose based on the severity of liver dysfunction and individual
tolerance to treatment.
Maximum dose: the daily dose should not exceed 1200 mg.
Method of administration
Tablets should be swallowed whole during or immediately after meals, with an adequate amount
of water.
Use of a higher than recommended dose of Agapurin
If more than the recommended dose is taken, consult a doctor or pharmacist immediately.
Initial symptoms may include nausea, dizziness, tachycardia, hypotension, followed by fever,
agitation, hot flushes, loss of consciousness, reflex depression, seizures, and coffee-ground
vomiting (indicative of gastrointestinal bleeding). Treatment of overdose is symptomatic.
In case of overdose or accidental ingestion by a child, contact a doctor immediately.
Missed dose of Agapurin
If a dose is accidentally missed, take it as soon as possible. If it is almost time for the next dose,
take only the next dose at the scheduled time.
Do not take a double dose to make up for a missed dose.
Stopping Agapurin treatment
Do not discontinue the use of this medicine without consulting your doctor.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
Immediate medical attention must be sought if the patient develops:

symptoms of anaphylactic shock, disorientation and fainting (due to circulatory disturbances and drop in blood pressure) or anaphylactic reactions, such as raised, itchy rash (urticaria), facial swelling, eyelid swelling, lip swelling, swelling of the oral cavity, or breathing difficulties. These conditions may be life-threatening.
retinal haemorrhage

Prompt medical attention should be sought if the patient develops a tendency to bruising and bleeding, as these may be symptoms of thrombocytopenia (reduced platelet count). In such cases, blood morphology should be regularly monitored in patients treated with Agapurin.

Adverse reactions may occur with the following frequency:

Common (occurring in 1 to 10 patients per 100): nausea, vomiting, bloating, abdominal pain, diarrhoea.

Uncommon (occurring in 1 to 10 patients per 1,000): dizziness, headache, hot flushes, blurred vision.

Rare (occurring in 1 to 10 patients per 10,000): skin allergic reactions, erythema (redness of the skin), pruritus (itching), urticaria, increased sweating, cholestasis (bile stasis), increased liver enzyme activity (aminotransferases), hypotension (low blood pressure), tachycardia (accelerated heart rate), palpitations, cardiac arrhythmias, angina pectoris (chest pain), restlessness, sleep disturbances, hallucinations, hypoglycaemia (low blood glucose concentration), anaphylactic shock.

Very rare (occurring in fewer than 1 in 10,000 patients): aplastic anaemia, thrombocytopenia, haemorrhages (e.g. into the skin, mucous membranes, stomach, intestines).

Frequency not known (frequency cannot be estimated from available data): anaphylactic reaction, pseudoanaphylactic reaction, leukopenia or neutropenia, agitation, angioedema (swelling of various body parts, most commonly the face), rash, aseptic meningitis, gastrointestinal disorder, discomfort in the epigastrium, feeling of fullness in the abdomen (feeling of satiety), constipation, excessive salivation, decreased blood pressure, bronchospasm.

Reporting of adverse reactions

If any adverse reactions occur, including those not listed in this leaflet, they should be reported to a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Poland.

Tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl

Adverse reactions may also be reported to the marketing authorisation holder or its representative in Poland.

Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Agapurin

Keep the medicine out of the sight and reach of children.
Store below 25°C.
Do not use the medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What the medicine Agapurin contains
The active substance is pentoxifylline, 100 mg in each coated tablet.
The other ingredients are: monohydrate lactose, corn starch, talc, magnesium stearate,
anhydrous colloidal silicon dioxide. Coating: sodium carmellose, sucrose, talc, titanium dioxide,
anhydrous colloidal silicon dioxide, arabic gum, white wax and carnauba wax.
What Agapurin looks like and contents of the pack
Opalescent, white, biconvex coated tablets.
Pack size: 60 coated tablets.
Marketing Authorisation Holder
Zentiva a.s., Einsteinova 24, 851 01 Bratislava, Slovak Republic.
Manufacturer
Saneca Pharmaceuticals a.s., Nitrianska 100, 920 27 Hlohovec, Slovak Republic.
For further information, please contact the representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel.: +48 22 375 92 00