Pentoxifylline

Pharmacological properties

pentoxifylline improves the rheological properties of blood (fluidity), reducing the increased viscosity of the blood. Its pharmacological properties are explained by the fact that it:

• improves the deteriorated ability of red blood cells to deform by inhibiting PDE with a further increase in intracellular concentrations of cAMP and ATP, as well as inhibiting the aggregation of red blood cells;
• inhibits platelet aggregation;
• reduces pathologically high plasma fibrinogen levels;
• inhibits leukocyte activation and leukocyte adhesion to vascular endothelium. The effect of pentoxifylline on morbidity in cardiac or cerebrovascular pathologies and / or corresponding mortality has not been studied.

Pharmacokinetics The prolonged release of pentoxifylline from the drug occurs over 10-12 hours, and all this time in the blood its constant level is maintained. The released pentoxifylline is rapidly and almost completely absorbed. After this, a pronounced presystemic metabolism of the substance occurs, its systemic availability is only 20-30%. Pentoxifylline is almost completely metabolized in the liver. The main active metabolite 1- (5-hydroxyhexyl) -3, 7-dimethylxanthine (metabolite I) is in plasma in a concentration that is 2 times higher than the concentration of the starting substance with which it is in reverse biochemical equilibrium. In this regard, pentoxifylline and metabolite I are considered as an active unit. Excretion of pentoxifylline biphasic; initial T_½ for the starting material it is 0.4–0.8 hours, and for metabolites - 1.0–1.6 hours. Final T_½ pentoxifylline from blood plasma is approximately 1.6 hours. Excretion occurs mainly through the kidneys in the form of unconjugated water-soluble polar metabolites; only 4% comes with feces. In an unchanged state, pentoxifylline is excreted in trace amounts.

In patients with severe renal or hepatic dysfunction T_½ longer and absolute bioavailability increases.

Indications

Extension of the painless gait distance in patients with chronic occlusive lesion of the peripheral arteries at the iib stage of the fountain (intermittent claudication), when other measures, such as walking training, angioplasty and / or recovery procedures cannot be performed or are not indicated.

Inner ear dysfunction caused by circulatory disorders (including hearing loss and sudden hearing loss).

Application

Chronic occlusive disease of the peripheral arteries at the stage iic of the fountain (intermittent claudication).

Unless otherwise prescribed, then take 1 tablet of prolonged action of Agapurin SR 400 mg 3 times a day (equivalent to 1200 mg of pentoxifylline per day).

For patients with low or unstable blood pressure, dose adjustment is required.

The dose for patients with renal failure (creatinine clearance 30 ml / min) should be selected, taking into account individual tolerance.

For patients with severe liver dysfunction, it is necessary to reduce the dose according to the decision of the doctor, who in each case must take into account individually the severity of the disease and tolerance to the drug.

Inner ear dysfunction caused by circulatory disorders (including hearing loss and sudden hearing loss).

Unless otherwise prescribed, then take 1 tablet of prolonged action of Agapurin SR 400 mg 2 or 3 times a day (equivalent to 800–1200 mg of pentoxifylline per day).

For patients with low or unstable blood pressure, dose adjustment is necessary.

In patients with renal failure (creatinine clearance 30 ml / min), doses should be titrated to 50–70% of the standard dose, taking into account individual tolerance, for example, the use of pentoxifylline 400 mg 2 times a day instead of 400 mg 3 times a day.

In patients with severe liver dysfunction, the decision to reduce the dose should be made by the doctor, taking into account the severity of the disease and tolerability of the drug in each individual patient.

The method and duration of administration.

The dose of the drug Agapurin SR 400 mg is determined by the doctor, taking into account the individual characteristics of the patient. Typically, the drug Agapurin SR 400 mg is prescribed to adults 400 mg 2-3 times a day. The maximum daily dose should not exceed 1.2 g of pentoxifylline. Tablets should be taken after meals, without chewing, with a sufficient amount of liquid (approximately 100 ml).

For patients with a significant decrease in renal function (creatinine clearance of 30 ml / min), the dose can be reduced to 1-2 tablets per day. For patients with severe hepatic impairment, patients at particular risk for the consequences of lowering blood pressure (for example, with severe damage to the coronary vessels, severe stenosis of the cerebral vessels), it is necessary to start treatment with low doses, select doses individually and increase them gradually, taking into account treatment tolerance.

Note. In the case of accelerated passage through the gastrointestinal tract (the use of laxatives, diarrhea, surgical shortening of the intestine), in some cases, the removal of tablet residues may occur. If premature elimination occurs only occasionally, you should not pay much attention to this.

Contraindications

Hypersensitivity to pentoxifylline, other derivatives of methylxanthine or to any of the components of the drug. acute myocardial infarction. cerebral hemorrhage or other clinically significant bleeding. stomach and / or intestinal ulcers. hemorrhagic diathesis. retinal hemorrhage.

If hemorrhage in the retina occurs during treatment with pentoxifylline, the use of the drug should be stopped immediately.

Side effects

Side effects may occur during treatment with agapurinom 400 mg. side effects are classified by frequency: very often: ≥10%; often: ≥1% –10%; sometimes: ≥0.1% –1%; rarely: ≥0.01% –0.1%; very rare: 0.01%, including isolated cases.

Nervous system

Sometimes: dizziness, trembling, headache, fever, anxiety.

Rarely: sleep disorder, hallucinations.

Very rarely: increased sweating, paresthesia, cramps.

Symptoms of aseptic meningitis - patients with autoimmune diseases (systemic lupus erythematosus, mixed connective tissue disease) are prone to their occurrence. In all known cases, the symptoms disappeared after cessation of pentoxifylline.

The cardiovascular system

Sometimes: cardiac arrhythmia (e.g. tachycardia).

Rarely: decreased blood pressure, angina pectoris, palpitations, dyspnea, peripheral edema / angioedema.

Very rarely: increased blood pressure.

Gastrointestinal Disorders

Often: gastrointestinal upsets, in particular nausea, vomiting, flatulence, bloating, diarrhea.

Rarely: gastric and intestinal bleeding.

Violation of the liver and biliary tract.

Very rarely: stagnation of bile (intrahepatic cholestasis) and increased activity of liver enzymes (transaminases, alkaline phosphatase).

Metabolic and nutritional disorders

Rarely: hypoglycemia.

Skin, allergic reactions

Often: hot flashes.

Sometimes: hypersensitivity reactions - itching, erythema, urticaria.

Rarely: hemorrhages in the skin and mucous membranes.

Very rarely: severe hypersensitivity reactions that develop within a few minutes after the administration of pentoxifylline (angioedema, spasm of the bronchial muscles, anaphylactic shock); epidermal necrolysis and Stevens-Johnson syndrome.

In the event of the first signs of a hypersensitivity reaction, it is necessary to stop taking the drug and consult a doctor immediately.

Eye problems

Sometimes: visual impairment, conjunctivitis.

Very rare: retinal hemorrhage, retinal detachment.

If hemorrhage in the retina occurs during treatment with pentoxifylline, it is necessary to immediately stop the use of the drug.

Blood and lymphatic system

Rarely: urogenital hemorrhage.

Very rarely: intracranial bleeding, thrombocytopenia with thrombocytopenic purpura and aplastic anemia (partial or complete cessation of the formation of all blood cells, pancytopenia), fatal consequences are possible. Therefore, regular monitoring of the blood picture is necessary.

special instructions

The drug must be used under regular medical supervision. Particularly careful medical monitoring is necessary for patients with cardiac arrhythmias, arterial hypotension, coronary sclerosis, and those who have suffered heart attacks or surgery.

For patients with systemic lupus erythematosus or mixed connective tissue disease, pentoxifylline can be prescribed only after a thorough analysis of the ratio of possible risks and benefits.

Due to the risk of hemorrhage with the simultaneous use of pentoxifylline and oral anticoagulants, careful monitoring and frequent checks of blood sedimentation parameters are necessary.

Since there is a risk of developing aplastic anemia during treatment with pentoxifylline, regular monitoring of the general blood picture is necessary.

In patients with renal failure (creatinine clearance of 30 ml / min) or severe liver dysfunction, pentoxifylline excretion may be slowed down. Proper monitoring is required.

Patients with renal failure. For patients with renal failure (creatinine clearance 30 ml / min), titration of doses up to 50–70% of the standard dose should be carried out taking into account individual tolerance, for example, take 400 mg pentoxifylline 2 times a day instead of 400 mg 3 times a day.

Patients with severe liver dysfunction. In patients with severe liver dysfunction, the decision to reduce the dose should be made by the doctor, taking into account the severity of the disease and tolerance in each individual patient.

Use during pregnancy and lactation. Since there is insufficient experience with the use of pentoxifylline in pregnant women, it should not be prescribed during pregnancy.

During lactation, pentoxifylline passes into breast milk. Due to the lack of sufficient clinical experience with the use of the drug during breastfeeding, it is possible to use it if the doctor believes that the expected positive effect for the mother outweighs the potential risk for the baby.

Children. Due to the lack of sufficient clinical experience, Agapurin SR 400 mg should not be prescribed to children.

The ability to influence the reaction rate when driving vehicles or other mechanisms. Unknown: If dizziness and other adverse reactions occur during treatment with the drug, one should refrain from driving vehicles and working with mechanisms.

Interactions

Pentoxifylline potentiates the effect of anticoagulants, fibrinolytic drugs, enhances the action of antihypertensive (in particular APF inhibitors) drugs, nitrates and hypoglycemic agents (both insulin and oral antidiabetic drugs). careful monitoring of the health status of patients taking other drugs at the same time as pentoxifylline is necessary.

In some patients, the simultaneous use of pentoxifylline and theophylline can lead to an increase in theophylline levels, which can increase the number or increase the severity of side effects associated with theophylline.

Overdose

Symptoms: dizziness, nausea, decreased hell, tachycardia, hot flashes, unconsciousness, fever, agitation, areflexia, tonic-clonic convulsions, arrhythmia, vomiting in the form of "coffee grounds".

Treatment: if an overdose has occurred recently, you can conduct a gastric lavage or apply activated charcoal to prevent further absorption. Treatment should be symptomatic, as the specific antidote is unknown. In order to prevent complications, observation in the intensive care unit may be required.

Urgent measures in the event of severe hypersensitivity reactions (shock). At the first signs (for example, skin reactions (urticaria), flushing, anxiety, headache, sudden increase in perspiration, nausea), a venous catheter must be installed. Along with the usual emergency measures, such as placing the patient in a supine position with raised legs, ensuring patency of the airways and administering oxygen, emergency medication is indicated, in particular intravenous fluid volume replacement, epinephrine (adrenaline) iv, glucocorticoids ( for example, 250–1000 mg of iv methylprednisolone and histamine receptor antagonists.

Depending on the severity of the clinical symptoms, artificial respiration may be necessary, and in case of circulatory arrest, restoration of vital functions according to the usual recommendations.

Storage conditions

It does not need special storage conditions.