Package leaflet: Information for the user

Warning! Keep the leaflet! Information on the immediate packaging in a foreign language.
AGAPURIN SR 400 (АГАПУРИН SR 400 mg), 400 mg, prolonged-release tablets
Pentoxifyllinum
AGAPURIN SR 400 and АГАПУРИН SR 400 mg are different trade names of the same medicinal product,
written in Polish and Bulgarian languages.
Please read the leaflet carefully before use, as it contains
important information for the patient.

Keep this leaflet for future reference.
If you have any doubts, consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm another person, even if their symptoms are identical.
If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet:

What Agapurin SR 400 is and what it is used for
Important information before taking Agapurin SR 400
How to take Agapurin SR 400
Possible side effects
How to store Agapurin SR 400
Contents of the pack and other information

1. What Agapurin SR 400 is and what it is used for

Indications for Agapurin SR 400:

Peripheral arterial and arteriovenous circulation 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 disturbances of retinal and choroidal circulation);
Inner ear function disorders (hearing impairments, sudden hearing loss, etc.) caused by circulatory disturbances;
Cerebral ischemia (post-stroke conditions, vascular-origin brain dysfunction with symptoms such as lack of concentration, dizziness, memory disturbances, etc.).

Agapurin SR 400 is intended for use in adult patients.

2. Important information before using Agapurin SR 400

When not to use Agapurin SR 400

if the patient is allergic to pentoxifylline, other methylxanthines, or to any of the other ingredients of this medicine (listed in section 6);
if the patient has recently suffered an acute myocardial infarction or stroke;
if the patient has significantly increased bleeding or diseases with a high risk of haemorrhage;
if the patient has experienced retinal haemorrhage.

Warnings and precautions
Before starting treatment with Agapurin SR 400, discuss this with your doctor or pharmacist.
Your doctor should consider the benefit-risk ratio of using Agapurin SR 400 in patients with hypotension, severe cardiac arrhythmias, advanced atherosclerosis of coronary and cerebral vessels, acute myocardial infarction, diabetes mellitus, or severe renal impairment.
If symptoms of anaphylactic or pseudoanaphylactic reactions occur, treatment with Agapurin SR 400 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 SR 400.
Renal impairment (creatinine clearance < 30 ml/min) and severe hepatic dysfunction may delay the elimination of pentoxifylline.
In such cases, the dose of the medicine should be reduced and the patient should remain under continuous medical supervision.
Patients with an increased tendency to bleed who are taking Agapurin SR 400 concomitantly with vitamin K antagonists, antiplatelet agents, or antidiabetic medicines should be under continuous medical supervision.
Patients taking Agapurin SR 400 concomitantly with antidiabetic medicines should be under continuous medical supervision (see "Agapurin SR 400 with other medicines" below).
In patients with low blood pressure or heart disease, administration of Agapurin SR 400 may cause a sudden drop in blood pressure, and rarely, back pain or retrosternal pain.
Therefore, blood pressure should be monitored during treatment.
Patients taking Agapurin SR 400 concomitantly with ciprofloxacin should be under continuous medical supervision (see "Agapurin SR 400 with other medicines" below).
Patients taking pentoxifylline concomitantly with theophylline should be under continuous medical supervision (see "Agapurin SR 400 with other medicines" below).

Agapurin SR 400 with other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines you plan to take.
Agapurin SR 400 may enhance the effect of antihypertensive medicines (including angiotensin-converting enzyme inhibitors) or other medicines lowering blood pressure (e.g. nitrates).
In patients treated with insulin or oral antidiabetic medicines, administration of Agapurin SR 400 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, cases of enhanced anticoagulant effect have been reported. Close monitoring of anticoagulant activity is recommended when initiating or modifying the dose of Agapurin SR 400 in these patients.
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, or 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 lead to increased serum concentrations of pentoxifylline. Therefore, increased frequency and severity of adverse effects associated with concomitant use of these two active substances may occur.
Concomitant use of Agapurin SR 400 with cimetidine may increase plasma concentrations of pentoxifylline and its active metabolite.

Agapurin SR 400 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 have a child, she should consult her doctor before using this medicine.
Use of this medicine is not recommended in pregnant women or in 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 effect on the ability to drive or operate machinery.

3. How to use Agapurin SR 400

This medicine should always be used as directed by the physician. In case of doubt, consult your
doctor or pharmacist.
The usual dose is 1 tablet two or three times daily.
Patients with low or fluctuating blood pressure may require a special dosing regimen.

Dosing in patients with renal function impairment
In patients with impaired renal function (creatinine clearance < 30 ml/min), the physician will reduce
the dose to 50–70% of the normally recommended dose and may recommend administering 1 or 2 tablets daily, depending on individual tolerance to treatment.

Dosing in patients with hepatic function impairment
In patients with severe liver insufficiency, dose reduction is necessary.
The treating physician will determine the appropriate dose based on the severity of liver impairment and individual tolerance to treatment.

Other
In patients with severe circulatory disorders, the effect of pentoxifylline may be enhanced by
concomitant administration of Agapurin SR 400 and pentoxifylline as an intravenous infusion.

Use in children and adolescents
There is no experience with use in children.

Method of administration
Tablets should be swallowed whole during or immediately after meals, with an adequate amount of
water.

Taking more Agapurin SR 400 than recommended
If you take more than the recommended dose, seek immediate advice from your doctor or
pharmacist.
Initial symptoms may include nausea, dizziness, tachycardia, hypotension, followed by fever, agitation, hot flushes, loss of consciousness, reflex suppression, seizures, and coffee-ground vomiting (indicative of gastrointestinal bleeding). Treatment of overdose is symptomatic. The patient may require intensive medical care in hospital.
In case of overdose or accidental ingestion by a child, contact a doctor immediately.

Missed dose of Agapurin SR 400
If you accidentally miss a dose, take it as soon as possible. If it is almost time for the next dose, take only that dose at the scheduled time. Do not take a double dose to make up for a missed dose.

Stopping treatment with Agapurin SR 400
Do not discontinue treatment without consulting your doctor.

If you have any further questions regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Immediately consult a doctor if the patient experiences:

symptoms of anaphylactic shock, disorientation, or fainting (due to circulatory disturbances and low blood pressure) or anaphylactic reactions, such as raised, itchy rash (urticaria), swelling of the face, eyelids, lips, mouth, or difficulty breathing. These conditions may be life-threatening.
retinal haemorrhage.

Promptly consult a doctor if the patient develops a tendency to bruising or bleeding, as these may be symptoms of thrombocytopenia (reduced number of platelets). In such cases, blood morphology should be regularly monitored during treatment with Agapurin SR 400.
Gastrointestinal adverse effects are dose-dependent and usually resolve after discontinuation of treatment.
Adverse effects may occur with the following frequency:
Common (occurring in 1 to 10 patients out of 100): nausea, vomiting, bloating, abdominal pain, diarrhoea.
Uncommon (occurring in 1 to 10 patients out of 1,000): dizziness, headache, blurred vision, hot flushes.
Rare (occurring in 1 to 10 patients out of 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 (increased heart rate), palpitations (awareness of heart beating), cardiac arrhythmias, angina pectoris (chest pain), restlessness, sleep disturbances, hallucinations, hypoglycaemia (abnormally low blood glucose levels), anaphylactic shock.
Very rare (occurring in fewer than 1 in 10,000 patients): aplastic anaemia, thrombocytopenia, bleeding (e.g. into the skin, mucous membranes, stomach, intestines).
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 in 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 effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, telephone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Agapurin SR 400

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

6. Contents of the pack and other information

What Agapurin SR 400 contains
The active substance is pentoxifylline in an amount of 400 mg.
The other ingredients are:
core: hypromellose 2208/15000, povidone 30, talc, magnesium stearate;
coating: Sepifilm 752 white (hypromellose, microcrystalline cellulose, polyoxy 40 stearate,
titanium dioxide), simethicone emulsion SE4, macrogol 6000.
What Agapurin SR 400 looks like and contents of the pack
White, smooth, round, biconvex tablets.
Pack size: 20, 50 or 100 prolonged-release tablets in blister packs, in a cardboard box.
For further detailed information, please contact the Marketing Authorisation Holder or Parallel Importer.
Marketing Authorisation Holder in Bulgaria, country of export:
Zentiva, k.s., U Kabelovny 130, Dolní Měcholupy, 102 37 Prague 10, Czech Republic
Manufacturer:
Saneca Pharmaceuticals a.s., Nitrianska 100, 920 27 Hlohovec, Slovakia
Zentiva, k.s., U Kabelovny 130, Dolní Měcholupy, 102 37 Prague 10, Czech Republic
Parallel Importer:
InPharm Sp. z o.o., Strumykowa Street 28/11, 03-138 Warsaw, Poland
Repackaged by:
InPharm Sp. z o.o. Services sp. k., Chełmżyńska Street 249, 04-458 Warsaw, Poland
Marketing Authorisation Number in Bulgaria, country of export: 20060666
Parallel Import Licence Number: 347/24