AGAPURIN 400 mg Tablets

Contents of the leaflet

1. Leaflet attached to the packaging: information for the user
2. Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.
3. AGAPURIN SR 400 (Pentoxifylline SR Zentiva 400 mg)
   1. You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet:
4. What is Agapurin SR 400 and what is it used for
5. Important information before taking Agapurin SR 400
   1. When not to take Agapurin SR 400
   2. Warnings and precautions
   3. Agapurin SR 400 and other medicines
   4. Agapurin SR 400 with food and drink
   5. Pregnancy and breastfeeding
   6. Driving and using machines
6. How to take Agapurin SR 400
   1. Overdose of Agapurin SR 400
   2. Missed dose of Agapurin SR 400
   3. Discontinuation of Agapurin SR 400
7. Possible side effects
   1. Reporting side effects
8. How to store Agapurin SR 400
9. Contents of the packaging and other information
   1. What Agapurin SR 400 contains
   2. What Agapurin SR 400 looks like and what the packaging contains
   3. Marketing authorization holder in Romania, the country of export:
   4. Manufacturer:
   5. Parallel importer:
   6. Repackaged by:
   7. Parallel import authorization number: 577/12 Date of approval of the leaflet: 05.10.2022

Leaflet attached to the packaging: information for the user

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

AGAPURIN SR 400 (Pentoxifylline SR Zentiva 400 mg)

400 mg, prolonged-release tablets
Pentoxifylline
AGAPURIN SR 400 and Pentoxifylline SR Zentiva 400 mg are different trade names for the same medicine.

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to you specifically. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Agapurin SR 400 and what is it used for
• 2. Important information before taking Agapurin SR 400
• 3. How to take Agapurin SR 400
• 4. Possible side effects
• 5. How to store Agapurin SR 400
• 6. Contents of the packaging and other information

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

Indications for the use of Agapurin SR 400:

• peripheral arterial and arteriovenous circulatory disorders caused by atherosclerosis, diabetes, as well as disorders of inflammatory or functional origin; intermittent claudication or rest pain, diabetic angiopathy, obliterative vascular disease, trophic changes (post-thrombotic syndrome, leg ulcers, gangrene), angioneuropathies;
• circulatory disorders in the eye (acute and chronic circulatory disorders in the retina and choroid);
• disorders of the inner ear (hearing disorders, sudden hearing loss, etc.) caused by circulatory disorders;
• brain hypoxia (post-stroke conditions, cerebral functional disorders of vascular origin with symptoms such as lack of concentration, dizziness, memory disorders, etc.).

Agapurin SR 400 is intended for use in adult patients.

2. Important information before taking Agapurin SR 400

When not to take Agapurin SR 400

• if you are allergic to pentoxifylline, other methylxanthines, or any of the other ingredients of this medicine (listed in section 6);
• if you have recently had an acute myocardial infarction or stroke;
• if you have significantly increased bleeding and diseases with a high risk of bleeding;
• if you have had a retinal hemorrhage.

Warnings and precautions

Before starting treatment with Agapurin SR 400, you should discuss it with your doctor or pharmacist.
The doctor should consider the benefit-risk ratio of using Agapurin SR 400 in patients with arterial hypotension, severe heart rhythm disorders, advanced coronary and cerebral atherosclerosis, acute myocardial infarction, diabetes, and severe renal dysfunction.
If symptoms of anaphylactic or anaphylactoid reaction occur, you should discontinue use of Agapurin SR 400 and immediately contact your doctor.
During treatment with Agapurin SR 400, patients with severe heart rhythm disorders, advanced coronary and cerebral atherosclerosis with arterial hypotension, and post-myocardial infarction should be under constant medical supervision.
Renal dysfunction (creatinine clearance <30 ml min) and severe liver dysfunction may cause delayed elimination of pentoxifylline. in such cases, the dose medicine should be reduced, patient under constant medical supervision.
Patients with an increased tendency to bleeding, taking Agapurin SR 400 simultaneously with vitamin K antagonists, platelet aggregation inhibitors, or oral antidiabetic drugs, should be under constant medical supervision.
Patients taking Agapurin SR 400 simultaneously with oral antidiabetic drugs should be under constant medical supervision (see "Agapurin SR 400 and other medicines", below).
In patients with low blood pressure or heart disease, after administration of Agapurin SR 400, a sudden drop in blood pressure and, rarely, back pain or chest pain may occur. Therefore, during treatment, blood pressure should be monitored.
Patients taking Agapurin SR 400 simultaneously with ciprofloxacin should be under constant medical supervision (see "Agapurin SR 400 and other medicines", below).
Patients taking pentoxifylline simultaneously with theophylline should be under constant medical supervision (see "Agapurin SR 400 and other medicines").

Agapurin SR 400 and other medicines

You should tell your doctor about all medicines you are currently taking or have 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 that lower blood pressure (e.g., nitrates).
In patients treated with insulin or oral antidiabetic drugs, after administration of Agapurin SR 400, a decrease in blood glucose levels may occur. Therefore, diabetic patients should be under constant medical supervision.
In patients taking pentoxifylline simultaneously with vitamin K antagonists, cases of increased anticoagulant effect have been reported. When starting or modifying the dose of Agapurin SR 400 in these patients, close monitoring of anticoagulant activity is recommended.
Due to the increased risk of bleeding, caution should be exercised in patients taking pentoxifyllines simultaneously with platelet aggregation inhibitors, such as clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, non-steroidal anti-inflammatory drugs other than selective COX-2 inhibitors, acetylsalicylic acid (aspirin) or lysine acetylsalicylate, ticlopidine, dipyridamole.
In some patients, concomitant use of pentoxifylline and theophylline may increase theophylline levels in the blood and enhance the adverse effects associated with its use.
In some patients, concomitant use of pentoxifylline and ciprofloxacin may increase pentoxifylline levels in the serum. Therefore, an increase in the frequency and severity of adverse effects associated with the concomitant use of these two active substances may occur.
Concomitant use of Agapurin SR 400 with cimetidine may increase pentoxifylline and its active metabolite levels in the blood.

Agapurin SR 400 with food and drink

See section 3.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor before taking this medicine.
This medicine is not recommended for use in pregnant or breastfeeding women.
In breastfeeding women, the doctor will decide whether the potential benefits outweigh the risks to the child.

Driving and using machines

This medicine has no influence on the ability to drive and use machines.

3. How to take Agapurin SR 400

This medicine should always be taken exactly as prescribed by your doctor. If you are unsure, you should consult your doctor or pharmacist.
The usual dose is 1 tablet 2 or 3 times a day.
Patients with low or variable blood pressure may require a special dosing schedule.
Dosing in patients with renal impairment
In patients with renal impairment (creatinine clearance <30 ml min), the doctor will reduce dose to 50-70% of usual recommended dose, depending on individual tolerance treatment, and recommend taking 1 or 2 tablets a day.
Dosing in patients with liver impairment
In patients with severe liver failure, the dose should be reduced. The decision on the dose to be used is made by the treating doctor, depending on the degree of liver failure and individual tolerance to treatment.
Other
In patients with severe circulatory disorders, the effect of pentoxifylline can be accelerated by concomitant administration of Agapurin SR 400 and pentoxifylline in the form of an intravenous infusion.
Use in children and adolescents
There is no experience with the use of Agapurin SR 400 in children.
Method of administration
Tablets should be swallowed whole during or immediately after a meal, with a sufficient amount of water.

Overdose of Agapurin SR 400

In case of overdose, you should immediately consult a doctor or pharmacist.
Initial symptoms may include nausea, dizziness, rapid heartbeat, hypotension, followed by fever, agitation, hot flashes, loss of consciousness, disappearance of reflexes, seizures, and hematemesis (vomiting blood associated with gastrointestinal bleeding). Treatment of overdose is symptomatic. The patient may require intensive medical care in a hospital.
In case of overdose or accidental ingestion of the medicine by a child, you should immediately consult a doctor.

Missed dose of Agapurin SR 400

In case of a missed dose, you should take it as soon as possible. If it is almost time for the next dose, you should take only that dose at the scheduled time. Do not take a double dose to make up for the missed dose.

Discontinuation of Agapurin SR 400

Without consulting a doctor, you should not discontinue treatment with Agapurin SR 400.
If you have any further doubts about the use of this medicine, you should consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, Agapurin SR 400 can cause side effects, although not everybody gets them.
You should immediately consult a doctor if you experience:

• symptoms of anaphylactic shock, disorientation, and fainting (due to circulatory disorders and a drop in blood pressure) or anaphylactoid reactions, such as hives, facial, eyelid, lip, oral, or respiratory tract edema. These conditions can be life-threatening.
• retinal hemorrhage.

You should immediately consult a doctor if you experience a tendency to bruise and bleed, as these may be symptoms of thrombocytopenia (reduced platelet count). In such cases, during treatment with Agapurin SR 400, the patient's blood morphology should be regularly monitored.
Gastrointestinal side effects are dose-dependent and usually disappear after discontinuation of treatment.
Side effects may occur with the following frequency:
Common (occurring in 1 to 10 patients in 100): nausea, vomiting, bloating, abdominal pain, diarrhea.
Uncommon (occurring in 1 to 10 patients in 1000): dizziness, headache, blurred vision, hot flashes.
Rare (occurring in 1 to 10 patients in 10,000): allergic skin reactions, flushing, itching, urticaria, increased sweating, cholestasis, increased liver enzyme activity, hypotension, tachycardia, palpitations, arrhythmias, angina pectoris, anxiety, sleep disorders, hallucinations, hypoglycemia, anaphylactic shock.
Very rare (occurring in less than 1 in 10,000 patients): aplastic anemia, thrombocytopenia, bleeding (e.g., into the skin, mucous membranes, stomach, intestines).
Unknown (frequency cannot be estimated from available data): anaphylactic reaction, anaphylactoid reaction, leukopenia or neutropenia, agitation, angioedema, rash, aseptic meningitis, gastrointestinal disorders, discomfort in the upper abdomen, feeling of fullness in the stomach, constipation, excessive salivation, hypotension, bronchospasm.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Aleje Jerozolimskie 181C
02-222 Warsaw
phone: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Agapurin SR 400

The medicine should be stored out of sight and reach of children.
Store in a temperature below 25°C, in the original packaging.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Agapurin SR 400 contains

The active substance of the medicine is pentoxifylline in the amount of 400 mg.
Other ingredients are: hypromellose 2208/15000, povidone 30, talc, magnesium stearate; coating:
Sepifilm 752 white (hypromellose, microcrystalline cellulose, polyoxyl 40 stearate, titanium dioxide (E 171)), simethicone emulsion SE4, macrogol 6000.

What Agapurin SR 400 looks like and what the packaging contains

White, smooth, round, biconvex tablets.
Pack size: 20, 50, or 100 prolonged-release tablets in blisters in a cardboard box.
For more detailed information, you should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in Romania, the country of export:

Zentiva a.s.
Einsteinova 24
85101 Bratislava
Slovak Republic

Manufacturer:

Saneca Pharmaceuticals a.s.
Nitrianska 100
92027 Hlohovec
Slovak Republic
Zentiva, k.s.
U kabelovny 130, Dolní Měcholupy
102 37, Prague 10
Czech Republic

Parallel importer:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Romanian marketing authorization number, country of export: 9191/2016/01
9191/2016/02
9191/2016/03

Parallel import authorization number: 577/12 Date of approval of the leaflet: 05.10.2022

[Information about the trademark]