Pentoxifylline-NAN

Pentoxifylline

3.7-dimethyl-1-(5-oxohexyl)-3.7-dihydro-1H-purine-2.6-dione.

Enteric-coated tablets, 100 mg.

White enteric-coated biconvex tablets.

Each tablet contains:
Active substance: pentoxifylline, 100 mg.
Excipients: lactose monohydrate, potato starch, stearic acid, Acryl-EZE (including a copolymer of methacrylic acid with ethyl acrylate, talc, triethyl citrate, sodium lauryl sulfate, sodium carbonate, anhydrous colloidal silicon dioxide, titanium dioxide E171).

Purine derivatives.

C04AD03

Pentoxifylline is a derivative of methylxanthine. It improves the rheological properties of blood, reducing increased viscosity. Pentoxifylline, inhibiting phosphodiesterase with a subsequent increase in intracellular cAMP and ATP, improves the ability of red blood cells to deform and prevents their aggregation. It exhibits an antithrombotic effect by inhibiting platelet aggregation and reducing pathologically elevated levels of fibrinogen in blood plasma. It prevents activation of leukocytes and adhesion of leukocytes to the vascular endothelium.
There are no studies on the effect of pentoxifylline on cardiac and cerebrovascular morbidity and/or mortality.

• Chronic peripheral arterial occlusive disease, Fontaine stage IIb, intermittent claudication (in cases where other measures, such as therapeutic walking, angioplasty and/or recovery procedures are not possible).
• Dysfunction of the inner ear caused by circulatory disorders (including impairment of hearing and sudden hearing loss).
• Additional symptomatic treatment of pathological cognitive deficiency in elderly patients (with the exception of Alzheimer’s disease and other types of dementia).

Enteric-coated tablets are taken orally during or immediately after a meal. Swallow them whole with plenty of water.
Dosage and duration of administration are determined individually by the healthcare provider.
The initial dose is usually 100 mg (1 tablet) 3 times a day, followed by an increase in dose to 200 mg (2 tablets) 2-3 times a day.
The maximum single dose is 400 mg. The maximum daily dose (both orally and parenterally) should not exceed 1200 mg.
Due to the risk of arterial hypotension, patients with low or unstable blood pressure begin treatment with small doses, followed by a gradual increase in dose when necessary.

Patients with impaired renal function
In case of impaired renal function (creatinine clearance <30 ml/min), the dose should be reduced to 50-70% of the standard, depending on individual tolerance. The daily dose can be reduced to 100-200 mg and should not exceed 800 mg.

Patients with impaired liver function
In case of severe hepatic impairment, a dose reduction is required, taking into account individual tolerability.

Elderly patients
Given that the elimination rate may decrease in elderly patients, caution is advised, if necessary, adjusting the dose depending on the severity of the disease and the tolerability of Pentoxifylline-NAN.

Children and adolescents
Pentoxifylline-NAN is not prescribed to children due to lack of sufficient clinical experience.

If you miss an intake of Pentoxifylline-NAN, it should be taken as soon as possible. Do not take a double dose to make up for a missed one.

The following adverse reactions have been reported during clinical trials and post-marketing surveillance.

The following categories are used to indicate the frequency of adverse events:
Very common (≥1/10);
Common (≥1/100, <1/10);
Uncommon (≥1/1000, <1/100);
Rare (≥1 /10000, <1/1000);
Very rare (<1/10000);
Not known (frequency cannot be estimated from the available data).

Blood and lymphatic system disorders
Very rare: thrombocytopenia, thrombocytopenic purpura, and potentially fatal aplastic anemia (pancytopenia).
Not known: leukopenia/neutropenia.
Regular monitoring of the complete blood count is recommended.
Very rare: severe anaphylactic or anaphylactoid reactions that develop within a few minutes after taking pentoxifylline, such as angioedema, bronchospasm, or anaphylactic shock.
At the first signs of a hypersensitivity reaction, you should immediately stop taking Pentoxifylline-NAN and inform your healthcare provider.

Mental disorders
Uncommon: agitation, and/or sleep disturbance.

Nervous system disorders
Uncommon: dizziness, tremor, and headache.
Very rare: paresthesia, convulsions, intracranial hemorrhage.
Symptoms of aseptic meningitis: patients with autoimmune diseases (SLE, mixed connective tissue diseases) are prone to these symptoms. In all observed cases, the symptoms were reversible after discontinuation of pentoxifylline.

Eye disorders
Uncommon: visual disturbances, and conjunctivitis.
Very rare: retinal hemorrhage, and retinal detachment.
In case of retinal hemorrhage during therapy with pentoxifylline, you should immediately stop taking Pentoxifylline-NAN.

Heart disorders
Uncommon: cardiac arrhythmia (e.g. tachycardia).
Rare: angina pectoris, and dyspnoea.

Vascular disorders
Common: hot flashes.
Rare: bleeding (see adverse reactions for various organs).

Gastrointestinal disorders
Common: nausea, vomiting, bloating, heaviness in the stomach, and diarrhea.
Rare: gastric and intestinal bleeding.
Not known: constipation, and increased salivation.

Liver and biliary tract disorders
Very rare: intrahepatic cholestasis, elevated liver enzymes (see Laboratory and instrumental investigations).

Skin and subcutaneous tissue disorders
Uncommon: itching, redness, and allergic rash.
Rare: hemorrhages in the skin and subcutaneous tissues.
Very rare: epidermal necrolysis, Stevens-Johnson syndrome, and sweating.
Not known: rash.

Renal and urinary tract disorders
Rare: urinary bleeding.

Laboratory and instrumental investigations
Rare: low blood pressure, and decreased prothrombin time.
Very rare: increased transaminases or alkaline phosphatase, and high blood pressure.

General disorders
Uncommon: fever.
Rare: peripheral edema.

In case of side effects, it is necessary to stop taking Pentoxifylline-NAN. Patients should inform their healthcare providers in case of side effects, including those not mentioned in this leaflet.

Hypersensitivity to pentoxifylline and other xanthine derivatives, acute myocardial infarction, severe cardiac arrhythmia, massive bleeding, hemorrhagic stroke, retinal hemorrhage, hemorrhagic diathesis, gastric and/or intestinal ulcers, pregnancy, lactation, age up to 18 years (efficacy and safety have not been studied).

Symptoms
Dizziness, nausea, hypotension, tachycardia, flushing, loss of consciousness, fever, agitation, lack of reflexes, tonic-clonic convulsions, coffee-grounds vomiting, and arrhythmia.

Treatment
Taking of Pentoxifylline-NAN should be stopped immediately when the first signs of an overdose appear (sweating, nausea, or cyanosis). Provide a lower position of the head and upper body. Monitor free airway patency.
If a little time has passed after an overdose, gastric lavage and intake of activated charcoal are recommended.
Since the specific antidote is unknown, treatment is symptomatic under the control of the state of the cardiovascular system. In order to avoid complications, observation in the intensive care unit may be required.

Potential additive effect with inhibitors of platelet aggregation: due to the high risk of bleeding, one should be careful with simultaneous intake of pentoxifylline with inhibitors of platelet aggregation (such as clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, and NSAIDs other than selective COX-2 inhibitors, acetylsalicylates, ticlopidine, dipyridamole).

Anticoagulant activity should be monitored in patients taking pentoxifylline concomitantly with antivitamin K.
Simultaneous administration of ciprofloxacin and pentoxifylline can lead to an increase in the serum concentration of pentoxifylline.
It increases the effectiveness of antihypertensive drugs (including ACE inhibitors), insulin and oral hypoglycemic drugs (increased risk of hypoglycemia). The risk of hypotension increases when used together with medicinal products that can cause a decrease in blood pressure (for example, medicines containing nitro compounds).

Cimetidine increases the plasma concentration of pentoxifylline (risk of side effects).
It is not recommended to take pentoxifylline simultaneously with ketorolac, as the risk of bleeding and/or prolongation of prothrombin time increases.
Simultaneous administration of pentoxifylline and theophylline may lead in some patients to an increase in theophylline plasma concentration, and a subsequent increase in the side effects of theophylline.

Erythromycin: There is no evidence of a possible interaction between pentoxifylline and erythromycin. However, simultaneous administration of erythromycin and theomycin leads to a significant increase in the level of theophylline in the blood serum, accompanied by toxic reactions.
Sympathomimetics and xanthines: simultaneous administration with other xanthines or with sympathomimetics can lead to excessive stimulation of the central nervous system.

In the case of the use of Pentoxifylline-NAN in patients with chronic heart failure, the phase of circulatory compensation should first be reached.
At the first sign of anaphylactic/anaphylactoid reactions, discontinue treatment and seek medical attention.
In patients with systemic lupus erythematosus or other diseases of connective tissue, pentoxifylline should be prescribed only after a thorough analysis of all possible risks and benefits.
When using high doses of Pentoxifylline-NAN, the effect on blood sugar levels can be amplified in diabetic patients that receive insulin treatment or take oral hypoglycemic agents (see Section Interaction with other medicines). In these cases, the dose of insulin or oral hypoglycemic agents should be reduced and the patient should be monitored with particular care.
Since during treatment with pentoxifylline there is a risk of developing aplastic anemia, regular monitoring of the complete blood count is necessary.

Particularly careful monitoring is necessary for patients with:

• severe cardiac arrhythmias;
• arterial hypotension;
• severe atherosclerosis of the cerebral and coronary vessels;
• concomitant arterial hypertension;
• cardiac arrhythmias (attacks of angina pectoris, arrhythmias and a sharp increase in blood pressure are possible in these patients when taking Pentoxifylline-NAN);
• renal insufficiency (creatinine clearance less than 30 ml/min);
• severe liver failure;
• high bleeding tendency due to treatment with anticoagulants or blood clotting disorders, for example (see Section Contraindications);
• pre-existing gastric and duodenal ulcers;

And for patients who simultaneously receive treatment with pentoxifylline and antivitamin K (see Section Interaction with other medicines).

Pentoxifylline-NAN contains lactose, so patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not take Pentoxifylline-NAN.

Treatment should be carried out alongside with systematic control of blood pressure.

When administered simultaneously with anticoagulants, it is necessary to carefully monitor the indicators of the blood coagulation system. Pentoxifylline should be used with caution in patients with impaired blood clotting (increased risk of bleeding).

The administered dose should be reduced in patients with low and unstable blood pressure.

Smoking may reduce therapeutic efficacy of Pentoxifylline-NAN.

It is necessary to systematically monitor the parameters of the blood coagulation system (INR) in patients who have recently undergone surgery.

Pentoxifylline is not recommended during pregnancy. Pentoxifylline gets into breast milk in small amounts. Due to insufficient experience, it is necessary to weigh the possible risks and benefits when prescribing pentoxifylline in women who are breastfeeding.

Due to the possible occurrence of dizziness, it is recommended to be careful when driving vehicles and servicing complex mechanisms.
Drinking alcohol is not recommended while taking Pentoxifylline-NAN.

25 tablets in a blister pack. 3 blister packs with a patient information leaflet in a carton pack.

Protect from light and moisture. Store at a temperature not exceeding 25°C. Keep out of the reach of children.

2 years. Do not use after the expiration date.

State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus
Phone / Fax +375 17 268 63 64
production@academpharm.by
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en