Pentoxifylline

Pentoxifylline has vasodilating activity in relation to peripheral vessels.

The drug is a methylxanthine derivative. Its principle of action is based on the suppression of PDE action and the accumulation of cAMP inside blood cells and vascular smooth muscle cells, as well as inside other organs and tissues. [ 1 ]

The drug increases the flexibility of red blood cells with platelets and slows down their aggregation, reduces increased plasma fibrinogen values and potentiates fibrinolysis, due to which blood viscosity is weakened and rheological blood parameters are improved. [ 2 ]

Indications Pentoxifylline

It is used in case of such disorders:

• encephalopathy of atherosclerotic or cerebrovascular nature;
• cerebral form of ischemic stroke;
• a disorder of peripheral blood flow caused by the development of atherosclerosis, inflammation or diabetes mellitus (this also includes diabetic angiopathy);
• angioneuropathy ( Raynaud's syndrome );
• tissue lesions of a trophic nature caused by venous disease or microcirculation disorder (trophic ulcers, frostbite, post-thrombophlebitic syndrome or gangrene);
• endarteritis, which has an obliterating form;
• disorders of intraocular blood flow (subacute, acute or chronic insufficiency of blood flow within the retina or choroid);
• problems with the functioning of the inner ear, which have a vascular etiology (in this case, hearing loss develops).

Release form

The medicinal element is released in tablets - 10 pieces in a cell pack; there are 5 such packs in a box.

Pharmacodynamics

Pentoxifylline can cause the development of a minor vasodilating effect, which has a myotropic nature. At the same time, it slightly weakens the systemic resistance of peripheral vessels and causes a positive inotropic effect.

The use of the drug leads to an improvement in microcirculation processes and oxygen supply to tissues (mainly within the central nervous system with the extremities; a weaker effect is exerted relative to the kidneys). The drug causes some expansion of the coronary vessels. [ 3 ]

Pharmacokinetics

The main metabolic component demonstrating pharmacological action (1-(5-hydroxyhexyl)-3,7-dimethylxanthine) is found in blood plasma in values that are twice as high as the level of the unchanged element and is in a state of inverse biochemical balance relative to it. For this reason, the active substance of the drug with its metabolite is considered as an active whole.

The half-life of pentoxifylline is 1.6 hours. The drug participates fully in metabolic processes; over 90% of the drug is excreted through the kidneys (in the form of non-conjugated, water-soluble polar metabolic elements). Less than 4% of the applied dosage is excreted with feces.

In people with severe renal dysfunction, a slowdown in the excretion of the metabolic components of the drug is observed.

In individuals with liver dysfunction, the half-life of pentoxifylline is prolonged.

Dosing and administration

Pentoxifylline is used in the amount of 2-4 tablets, 2-3 times a day. Tablets are taken after meals, without chewing and washed down with plain water. A maximum of 1200 mg of the drug is allowed per day.

People with unstable or decreased blood pressure or with significant weakening of renal function (CC indicator below 30 ml per minute) and people from the group with a high risk of complications with a decrease in blood pressure (for example, in the case of severe damage in the coronary vessels or intense stenosis of the main cerebral vessels) need to start therapy with minimal dosages. Portions are selected individually, and their increase is carried out gradually, taking into account the tolerability of the therapy.

• Application for children

There is no experience of using the drug in pediatrics.

Use Pentoxifylline during pregnancy

There is only limited experience with the use of Pentoxifylline during pregnancy, which is why it is not prescribed during this period.

The drug is excreted in small amounts in breast milk, and therefore it is necessary to stop breastfeeding during the period of therapy.

Contraindications

Among the contraindications:

• severe intolerance to pentoxifylline, other methylxanthines or auxiliary components of the drug;
• presence of heavy bleeding (there is a possibility of increased bleeding);
• severe hemorrhage in the area of the retina or intracerebral hemorrhage (there is a risk of potentiation of bleeding). If hemorrhage in the area of the retina develops during the use of the drug, it is necessary to immediately stop taking it;
• active phase of myocardial infarction;
• ulcerative lesions in the gastrointestinal tract;
• diathesis that has a hemorrhagic form.

Side effects Pentoxifylline

Main side effects:

• disorders in the functioning of the cardiovascular system: tachycardia, hot flashes, decrease or increase in blood pressure, arrhythmia, peripheral edema and angina pectoris;
• problems with hematopoietic function: bleeding, aplastic anemia, neutro- or leukopenia, pancytopenia, which can lead to death, as well as thrombocytopenia together with thrombocytopenic purpura;
• disorders of the nervous system: headaches, paresthesia, hallucinations, dizziness and convulsions, as well as sleep disorders, agitation, tremors and aseptic meningitis;
• lesions affecting the gastrointestinal tract: a feeling of pressure in the stomach, vomiting, hypersalivation, gastrointestinal disorders, nausea, constipation, bloating and diarrhea;
• symptoms associated with the subcutaneous layer and epidermis: urticaria, redness, itching, rash, SJS and TEN;
• immune disorders: bronchial spasm, anaphylactic or anaphylactoid symptoms, anaphylaxis and Quincke's edema;
• problems with the functioning of the bile ducts and liver: intrahepatic cholestasis;
• visual disturbances: conjunctivitis, retinal detachment or hemorrhage, and visual dysfunction;
• changes in test results: increased transaminase values;
• Others: development of hyperhidrosis or hypoglycemia and an increase in temperature.

Overdose

Early signs of acute intoxication include dizziness, nausea, or decreased blood pressure. Along with this, the following symptoms may appear: agitation, tachycardia, arrhythmia, hot flashes, fever, areflexia, and tonic-clonic seizures. Loss of consciousness and vomiting of a dark brown color (a symptom of bleeding in the gastrointestinal tract) may also occur.

Elimination of acute poisoning and prevention of the development of complications is carried out by carrying out symptomatic procedures and intensive specific medical monitoring of the patient's condition.

Interactions with other drugs

The antidiabetic effect that develops when using hypoglycemic drugs for oral administration, as well as insulin, can be potentiated when administered with medication. Because of this, people treating diabetes mellitus should be under constant medical supervision.

Postmarketing studies have shown an increase in the anticoagulant effect in individuals using the drug together with vitamin K antagonists. The anticoagulant effect of such combinations should be monitored when prescribing or changing the dosage of Pentoxifylline.

The drug may potentiate the antihypertensive properties of antihypertensive substances and other drugs that can lead to a decrease in blood pressure values.

The use of the drug together with theophylline may cause an increase in the blood counts of the latter in some individuals. Because of this, the severity and frequency of the development of theophylline side effects may increase.

In some patients, administration together with ciprofloxacin causes an increase in the serum level of pentoxifylline. Because of this, the intensity of side effects may increase and their frequency of development may increase.

In theory, an additive effect may develop when using substances that slow platelet aggregation. Due to the increased likelihood of bleeding, combining these substances (including tirofiban, clopidogrel with iloprost, anagrelide, ticlopidine, and eptifibatide with abciximab, as well as dipyridamole, epoprostenol, NSAIDs (excluding selective COX-2 inhibitors), and acetylsalicylates) with the drug should be done with extreme caution.

Use in combination with cimetidine may cause an increase in plasma levels of pentoxifylline along with its metabolic unit I.

Storage conditions

Pentoxifylline should be stored in a place out of reach of small children. Temperature values should not exceed 25ºС.

Shelf life

Pentoxifylline can be used within a 36-month period from the date of sale of the therapeutic product.

Analogues

The analogs of the drug are Trental, Latren with Vazonit, Pentoxipharm and Agapurin with Xanthinol nicotinate, as well as Flexital, Pentilin and Trentan.