Trental of the tab. of p/o of 100 mg No. 60

Pharmacological properties

Pentoksifillin (3.7-dimetil-1-(5 oxohexyl) - 3.7-dihydro-1n-purine-2.6-dion) — derivative methylxanthine. the mechanism of action of a pentoksifillin is caused by oppression fde and accumulation tsamf in cells of unstriated muscles of vessels, blood cells and also in other fabrics and bodies. pentoksifillin slows down aggregation of thrombocytes and erythrocytes, increases their elasticity, reduces the increased concentration of fibrinogen in blood plasma and strengthens a fibrinolysis, promoting decrease in viscosity of blood and improvement of its rheological properties. besides, pentoksifillin has mild myotropic vasodilating effect, slightly reduces opss and renders positive inotropic effect. owing to use of a pentoksifillin the microcirculation and supply of fabrics with oxygen, more in extremities, central nervous system improves, it is moderate — in kidneys. medicament slightly expands coronary vessels.

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After intake in a dose of 100 mg pentoksifillin it is almost completely absorbed in a digestive tract. The maximum concentration of a pentoksifillin and its main metabolite is reached in 1 h after reception. Drug has effect of primary passing through a liver. The bioavailability of a pentoksifillin averages 19% (6–32%). The main pharmacological an active metabolite 1-(5 hydroxyhexyl) - 3.7 dimethylxantine are defined in blood plasma in concentration which exceeds twice concentration of not changed substance and is with it in a condition of the return biochemical balance. In this regard pentoksifillin and its metabolite it is necessary to consider as active whole. Elimination half-life of a pentoksifillin makes 1.6 h Pentoksifillin is metabolized completely, 90% are removed by kidneys in the form of not conjugated water-soluble polar metabolites. Less than 4% of the entered dose are removed with a stake. At patients with the profound renal failure the excretion of metabolites is slowed down. At patients from the liver broken by function note increase in elimination half-life of a pentoksifillin and increase in its bioavailability.

Indication

Atherosclerotic encephalopathy, an ischemic stroke, distsirkulyatorny encephalopathy, the disturbances of peripheric circulation caused by atherosclerosis, diabetes, inflammation; the trophic disturbances of fabrics caused by damage of arteries or veins, microcirculation disturbance (posttromboflebitichesky syndrome, trophic ulcers, gangrene, freezing injury); obliterating endarteritis; angioneyropatiya (Raynaud's disease, paresthesia); disturbance of blood circulation of an eye (an acute, subacute and chronic circulatory unefficiency in a retina and a choroid); dysfunctions of an inner ear of vascular character which are followed by relative deafness.

Use

trental Dose for in/in infusion — 100–600 mg (in 250–500 ml of solution of a ringer of a lactate, infusional solution or 5% of solution of glucose) 1 or 2 times a day. duration in/in infusions from 60 to 360 min., that is introduction of 100 mg of a pentoksifillin not less than 60 min. have to last infusion can be complemented with oral administration of trental.

If the condition of the patient heavy (constant pain, gangrene, trophic ulcers), is possible carrying out in/in infusion of Trental for 24 h. The dose is entered at the rate of 0.6 mg/kg/h. The daily dose for the patient with the body weight of 70 kg makes 1000 mg, for the patient with the body weight of 80 kg — 1150 mg. Irrespective of body weight the maximum daily dose makes 1200 mg. The volume of the entered solution is calculated individually taking into account associated diseases, a condition of the patient and averages 1.0-1.5 l/days

Trental Dose for jet in/in introductions is 100 mg. Introduction carry out slowly (not less than within 5 min.) 1–2 times a day. The patient shall be in a prone position.

Orally Trental are appointed in a dose on 2–4 tablets by 2–3 times a day after a meal without chewing, washing down with enough liquid.

Maximum total daily dose at parenteral and oral administration makes 1.2 g

Contraindication

Hypersensitivity to a pentoksifillin and other derivatives of methylxanthine, massive bleeding, a hemorrhagic stroke, a massive retinal apoplexy, an acute myocardial infarction, the period of pregnancy and feeding by a breast.

Side effects

Nausea, vomiting, weight in epigastric area, diarrhea, a headache, dizziness, aseptic meningitis (at reception in high doses), the concern, sleep disorders, a dermahemia of the person, rushes of blood, tachycardia, stenocardia, arterial hypotension, a skin itching, rash, a small tortoiseshell, a Quincke's disease, is extremely rare — an acute anaphylaxis. very seldom, generally at simultaneous use with anticoagulants or antiagregant — bleedings (capillary of skin and mucous membranes, gastrointestinal). relationship of cause and effect of bleedings with intake of trental is not proved. in isolated cases the thrombocytopenia was noted.

Special instructions

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With care medicament to patients with the profound atherosclerosis of brain and coronary vessels, especially at accompanying ag, disturbances of a warm rhythm, stenocardia attacks and also to patients with arterial hypotension or labile hell. in these cases the dose of medicament should be raised gradually, especially at parenteral administration. also patients need care when prescribing medicament with a round ulcer of a stomach and duodenum in the anamnesis; to the patients who recently transferred surgery. in these cases the risk of developing of bleeding is increased therefore systematic control of level of hemoglobin and a hematocrit is necessary.

Before prescribing of Trental the patient with chronic heart failure should reach blood circulation compensation.

to Patients with the labile or lowered arterial blood pressure, the patient of risk group (significant damage of coronary arteries or the profound stenosis of the main vessels of a brain) treatment needs to be begun with

with prescribing of medicament in low doses, to select doses individually and to raise them gradually, taking into account shipping of treatment.

At patients with the diabetes receiving insulin therapy or treatment by oral gipoglikemiziruyushchy means at use of Trental in a high dose strengthening of influence of these medicaments on glucose level in blood is possible

. In these cases it is necessary to lower a dose of insulin or oral gipoglikemiziruyushchy means and to exercise regular clinical control.

In a renal failure (clearance of creatinine of 30 ml/min.) a dose of medicament is selected individually, lowering it approximately by 30–50%. In the profound liver failure it is also necessary to lower Trental dose depending on individual tolerance of drug.

Interaction

Trental exponentiates effect of heparin and fibrinolytic means and also strengthens action of a row antihypertensive (in particular inhibitors apf) and antidiabetic (both insulin, and peroral gipoglikemiziruyushchy) medicaments and also nitrates.

Overdose

nausea, dizziness, tachycardia, decrease hell Are possible

. further fever, excitement, a loss of consciousness, an areflexia, kloniko-tonic spasms, vomiting of color of a coffee thick as symptom of gastrointestinal bleeding are possible.

is not present

Specific antidote. If from the moment of administration of medicament there passed a little time, gastric lavage and prescribing of activated carbon for prevention of further absorption of medicament is shown. Carry out symptomatic treatment.

Storage conditions

In the dark place at a temperature up to 25 °C.

Relevant information

Trental (pentoksifillin) — derivative methylxanthine with powerful haemo rheological properties (reduces viscosity of blood). medicine belongs to the medicaments influencing a cardiovascular system enters into group "peripheral vazodilatator".

Pentoksifillin is approved by

to appointment for treatment of persons with the alternating lameness in connection with an occlusal disease of peripheral arteries. Drug for the first time went on sale in Europe in 1972 and in the United States in 1985. Researches on animals and people showed haemo rheological and immunomodulatory properties.

Pharmacological Pharmacokinetics properties

Drug is easily soaked up by

from a GIT, but is exposed to primary metabolism in a liver. A part of its metabolites are active. It is reported that the seeming elimination half-life of a pentoksifillin from blood plasma — 0.4-0.8 h; at metabolites it fluctuates within 1.0-1.6 h. The most part of a dose of medicament is removed with urine, mainly in the form of metabolites, and less than 4% are allocated with a stake.

Adverse side effects

Drug Trental can make sick, gastrointestinal disorders (nausea, vomiting, diarrhea), dizziness, a headache, a tremor. These reactions are connected with a dose and at its decrease their expressiveness decreases. Also there can be inflows, stenocardia, heartbeat, cardiac arrhythmias and reactions of hypersensitivity. About cases of bleeding it was reported seldom, usually in connection with risk factors of developing of bleeding. Also at overdose of a pentoksifillin the fever, weakness, rushes of blood, arterial hypotension, drowsiness, excitement and spasms are possible.

Interactions

Trental (pentoksifillin) can strengthen effect of hypotensive drugs. High parenteral doses of a pentoksifillin can strengthen effect of insulin and hypoglycemic medicaments at patients with diabetes. Pentoksifillin it is not necessary to appoint with ketorolaky as there is an increased risk of bleeding and/or lengthening of a prothrombin time. Also there can be an increased risk of bleedings when using a meloksikam. Pentoksifillin can increase theophylline level in blood serum.

Use

Pentoksifillin is appointed at treatment of diseases of peripheral vessels. Though medicament is often classified as vasodilator, its main action, apparently, consists in decrease in viscosity of blood probably due to impact on erythrocytes, adhesion and aggregation of thrombocytes. It is reported that it increases inflow of blood to ischemic fabrics and improves their oxygenation at patients with a disease of peripheral vessels and increases oxygen content, it was applied in cerebrovascular disorders. Trental alpha also inhibits production of cytokine, tumor necrosis factor (TNF α), and this its property is studied in a number of diseases.

Pentoksifillin is entered parenterally at the beginning of therapy (in/in infusion which lasts 60–360 min.; if the condition of the patient is estimated as heavy, then infusion can be carried out for 24 h. In certain cases the medicament can be administered in a look in/in an injection. The dose of medicament is calculated individually and depends on many factors. After improvement of a condition of the patient it is recommended to carry out therapy using the tableted dosage form. At treatment of diseases of peripheral vessels a usual oral dose — 400 mg 3 r / days in shape with the modified release. The dose can be lowered to 400 mg 2 r / days (as maintenance therapy). The medicament should be taken at meal time for reduction of risk of gastrointestinal disorders. At severe forms of a liver or renal failure the dose decline also can be required. Favorable effects can be not obvious until 2-8 weeks therapy is carried out.

Renal, liver failure

Producers from Great Britain claim that for patients with heavy abnormal liver functions the dose decline of a pentoksifillin whereas accumulation can happen at patients to a heavy renal failure (the clearance of creatinine (CC) less than 30 ml/min.) can be required who receive more than 400 mg 1–2 r / days

Venous ulcers standing

Systematic overview of the pentoksifillin used at treatment of venous ulcers standing showed that it is effective addition to a compression bandage and can be effective even independently (D. Wylie, 2007).

In the United States of America this connection is appointed for treatment of the alternating lameness. Researches in public and animals showed that therapy by medicament leads to various physiological changes at the cellular level which can be important at treatment of various groups of diseases of the person. Immune modulation (process of change of one or several parameters) includes the increased deformability of leukocytes and a chemotaxis, decrease in adhesion of endothelial leukocytes, reduction of degranulation of neutrophils and release of superoxides, decrease in development of a factor of necrosis of tumors from monocytes, decrease in sensitivity of leukocytes to interleukin-1 and a factor of necrosis of tumors, inhibition of lymphocytes of T and In and decrease of the activity of natural cells killers. Hypercoagulative states improve due to reduction of aggregation and adhesion of thrombocytes, increase in plasminogen activator, increase in plasmin, antithrombin III, decrease in fibrinogen, alpha 2 - anti-plasmin, alpha 1 - antitrypsin and reduction alpha 2 - macroglobulin. Healing of wounds and disturbance of connective tissue — the response to increase in collagenases of fibroblasts and decrease in production of collagen, fibronectin and glikozaminoglikan. (Samlaska C.P., 1994).

Pentoksifillin is derivative methylxanthine which is used at disturbances of microcirculation as vasoactive medicine. It was reported about new immunomodulatory properties of a pentoksifillin, including decrease in regulation of synthesis of a factor of necrosis опухоли-α and other inflammatory cytokines. Researches showed what pentoksifillin can be effective at a wide range of skin diseases (Maakmak S.K., 2012).

Refractory or recurrent ulcers standing usually indicate

existence of the broken venous or arterial microcirculation (or both). According to a modern hypothesis, the local deficiency of oxygen and nutrients arises because gleams of capillaries are narrowed and become permeable for fibrinogen and proteins thanks to the activated leukocytes and an inadequate fibrinolysis. Adjournment of rather impenetrable perivascular fibrinous cover interfering adequate delivery of oxygen and nutrients results. Therefore therapy has to be directed to elimination of these shortcomings and improvement of healing of wounds. Pentoksifillin ( Trental ) applied in combination with topical treatment of wounds and the corresponding antibacterial therapy allowed to improve considerably healing of refractory ulcers standing. Pentoksifillin can change abnormal function of leukocytes and erythrocytes, thrombocytes and also to reduce viscosity of blood and permeability of vessels. Mechanisms of action of a pentoksifillin are described in the light of the modern hypotheses concerning development of an ulcer standing. Also nine cases when pentoksifillin at addition to earlier unsuccessful local care for a wound improved are discussed or cured refractory ulcers (Brenman S.A., 1991).

Venous ulcers standing are a widespread recurrent and disabling state. A basis of treatment is use of firm compression bandages or stockings for support of veins on a leg. Some ulcers standing heal within many months or years, and treatment is directed to prevention of an infection and acceleration of healing. Trental in the form of tablets is appointed for blood circulation improvement. The overview of researches shows that pentoksifillin, the pill of 400 mg taken 3 r / days increases recovery probability. Trental is effective addition to a compression bandage for treatment of venous ulcers. In the absence of a compression pentoksifillin it is also effective for treatment of venous ulcers. Gastrointestinal disorders (nausea, an indigestion and diarrhea) were the main side effects.

Ulcer standing are lower extremity wounds which did not heal within four-six weeks. It is considered that this disease affects about 1% of the population at some point of life, and there is it more often at women, than at men. About 50-70% of ulcers standing have venous origin.

Communication between insufficiency of gastrocnemius muscles and ulcerations is known to

long ago. Two hypotheses were made to explain the microcirculator changes observed at a venous ulceration. In the overview of 1982 it was suggested that venous hypertensia increases permeability of capillaries that leads to formation of the impenetrable perikapillyarny fibrinous cuff causing local fabric ischemia. However Coleridge Smith, 1988, claimed that the fibrinous cuff is secondary in relation to occlusion of capillaries traffic jams of white cells that creates distal ischemia. The taken white cells are released by agents who injure an endothelium, increasing permeability of capillaries and allowing to form a fibrinous cuff. Quite recently Koulridzh Smith assumed that infiltration of skin some proteinaceous products promotes destruction of fabrics.

Other Kokranovsky overview showed that compression therapy increases a share of the healed venous ulcers (O’Meara, 2012). Nevertheless, despite use of a compression, a part of venous ulcers remains not healing, and the therapy additional to a compression can be useful. Trental as addition to compression therapy in venous ulcers was a subject of researches during which contradictory results (Colgan, were received 1990; Dale, 1999). As standard therapy Trental was also compared to placebo without compression (Weitgasser, 1983; A.V. Jull et al., 2012).

Conclusion

Pentoksifillin was for the first time registered (in Germany) about 50 years ago. Then vasodilatation was its main action. Is later than haemo rheological effect, in particular on deformability of erythrocytes, it was not revealed. Irrespective of its pharmacological effects, clinical performance in diseases of peripheral and cerebral arteries is well-known. Through some period interested effect of the medicament Trental on leukocytes. It was reported as about rheological, and biochemical changes. Properties of this medicament are studied, also investigate its therapeutic potential therefore there is a probability that in the near future prescribing Trental will extend and will go beyond angiology.