Pharmacological properties of the drug Trental
Pentoxifylline (3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione) is a methylxanthine derivative. The mechanism of action of pentoxifylline is due to the inhibition of phosphodiesterase and the accumulation of cAMP in vascular smooth muscle cells, blood cells, as well as in other tissues and organs. Pentoxifylline inhibits the aggregation of platelets and erythrocytes, increases their elasticity, reduces the increased concentration of fibrinogen in the blood plasma and enhances fibrinolysis, helping to reduce blood viscosity and improve its rheological properties. In addition, pentoxifylline has a weak myotropic vasodilator effect, slightly reduces the peripheral vascular resistance and has a positive inotropic effect. Due to the use of pentoxifylline, microcirculation and oxygen supply to tissues improves, to a greater extent in the extremities, the central nervous system, and moderately in the kidneys. The drug slightly dilates the coronary vessels. After oral administration in a dose of 100 mg, pentoxifylline is almost completely absorbed in the digestive tract. The maximum concentration of pentoxifylline and its main metabolite is achieved 1 hour after administration. The drug has a first pass effect through the liver. The bioavailability of pentoxifylline averages 19% (6–32%). The main pharmacologically active metabolite 1-(5-hydroxyhexyl)-3,7-dimethylxanthine is determined in the blood plasma in a concentration that is 2 times higher than the concentration of the unchanged substance and is in a state of reverse biochemical equilibrium with it. In this regard, pentoxifylline and its metabolite should be considered as an active entity. The half-life of pentoxifylline is 1.6 hours. Pentoxifylline is completely metabolized, more than 90% is excreted by the kidneys in the form of unconjugated water-soluble polar metabolites. Less than 4% of the administered dose is excreted in the feces. In patients with severe renal impairment, the excretion of metabolites is slowed down. In patients with impaired liver function, an increase in the half-life of pentoxifylline and an increase in its bioavailability are noted.
Trental solution for injection 20 mg/ml ampoule 5 ml No. 5
Pentoxifylline increases the risk of developing arterial hypotension when used simultaneously with antihypertensive agents (for example, ACE inhibitors) or other drugs with a potential antihypertensive effect (for example, nitrates). Pentoxifylline may enhance the effect of drugs that affect the blood coagulation system (direct and indirect anticoagulants, thrombolytics, antibiotics such as cephalosporins). With the combined use of pentoxifylline and indirect anticoagulants (vitamin K antagonists), post-marketing studies have reported cases of increased anticoagulant action (risk of bleeding). Therefore, when starting to take pentoxifylline or when changing its dose, it is recommended to monitor the severity of the anticoagulant effect in patients taking this combination of drugs, for example, regularly monitor MHO. Cimetidine increases the concentration of pentoxifylline and active metabolite I in the blood plasma (risk of side effects). Co-administration with other xanthines may lead to excessive nervous stimulation. The hypoglycemic effect of insulin or oral hypoglycemic agents may be enhanced by simultaneous use of pentoxifylline (increased risk of hypoglycemia). Strict monitoring of the condition of such patients is necessary, including regular glycemic control. In some patients, with simultaneous use of pentoxifylline and theophylline, an increase in the concentration of theophylline in the blood is observed. This may subsequently lead to an increase or worsening of theophylline-related side effects. In some patients, with simultaneous use of pentoxifylline and ciprofloxacin, an increase in the concentration of pentoxifylline in the blood plasma is observed. In the future, this may lead to an increase or intensification of side effects associated with the use of this combination. With simultaneous use of pentoxifylline with platelet aggregation inhibitors (clopidogrel, eptifibatide, tirofiban, epoprostenol, iloprost, abciximab, anagrelide, NSAIDs [except selective COX-2 inhibitors], acetylsalicylic acid, ticlopidine, dipyridamole), a potential additive effect may develop, increasing the risk of bleeding . Therefore, caution should be exercised when using pentoxifylline simultaneously with the above platelet aggregation inhibitors.
Indications for use of the drug Trental
Atherosclerotic encephalopathy, ischemic stroke, dyscirculatory encephalopathy, peripheral circulatory disorders caused by atherosclerosis, diabetes mellitus, inflammation; trophic tissue disorders caused by damage to arteries or veins, microcirculation disorders (postthrombophlebitic syndrome, trophic ulcers, gangrene, frostbite); obliterating endarteritis; angioneuropathy (Raynaud's disease, paresthesia); circulatory disorders of the eye (acute, subacute and chronic circulatory failure in the retina and choroid); dysfunction of the inner ear of a vascular nature, accompanied by hearing loss.
Use of the drug Trental
The dose of Trental for intravenous infusion is 100-600 mg (in 250-500 ml of Ringer's lactate solution, infusion solution or 5% glucose solution) 1 or 2 times a day. The duration of the IV infusion is from 60 to 360 minutes, that is, the administration of 100 mg of pentoxifylline should last at least 60 minutes. The infusion can be supplemented with oral administration of Trental. If the patient's condition is severe (constant pain, gangrene, trophic ulcers), it is possible to administer an IV infusion of Trental for 24 hours. The dose is administered at the rate of 0.6 mg/kg/hour. The daily dose for a patient weighing 70 kg is 1000 mg, for a patient weighing 80 kg - 1150 mg. Regardless of body weight, the maximum daily dose is 1200 mg. The volume of the administered solution is calculated individually, taking into account concomitant diseases and the patient’s condition and averages 1.0 - 1.5 l/day. The dose of Trental for intravenous injection is 100 mg. Administration is carried out slowly (over at least 5 minutes) 1–2 times a day. The patient must be in a lying position. Orally Trental is prescribed in the following dose: 2-4 tablets 2-3 times a day after meals, without chewing, with a sufficient amount of liquid. The maximum total daily dose for parenteral and oral administration is 1.2 g.
TRENTAL
Directions for use and doses
The dose and route of administration are determined by the severity of circulatory disorders, as well as on the basis of individual tolerability of the drug Trental®.
The dosage is set by the doctor in accordance with the individual characteristics of the patient. The usual dose is from 100 mg to 600 mg of Trental® diluted in 250 ml or 500 ml of 0.9% sodium chloride solution or Ringer's solution, I or 2 times a day. Compatibility with other infusion solutions must be tested separately; Only clear solutions can be used. 100 mg of Trental® should be administered over at least 60 minutes.
In addition to infusion therapy, you can prescribe the drug Trental for oral administration. In this case, the total daily dose of Trental (intravenous infusion + oral administration) should not exceed 1200 mg.
Depending on concomitant diseases (for example, chronic heart failure), it may be necessary to reduce the injected volumes. In such cases, it is recommended to use a special infuser for controlled infusion.
In more severe cases, especially in patients with severe pain at rest, with gangrene or trophic ulcers (stages III-IV according to the Fontaine classification), long-term intravenous infusion of Trental® at a dose of 1200 mg over 24 hours is indicated. This dose can be divided into two 600 mg infusions, each administered over at least 6 hours. In this case, the individual dose can be calculated using the formula: 0.6 mg of pentoxifylline per kg of body weight per hour. The daily dose calculated in this way would be 1000 mg of pentoxifylline for a patient weighing 70 kg and 1150 mg of pentoxifylline for a patient weighing 80 kg.
During maintenance therapy, switch to taking the drug Trental orally.
In patients with renal failure (creatinine clearance less than 30 ml/min), it is necessary to reduce the dosage by 30-50%, which depends on the individual tolerability of the drug Trental® by the patient.
A dose reduction, taking into account individual tolerance, is necessary in patients with severe liver dysfunction.
Treatment can be started in low doses in patients with low blood pressure, as well as in patients at risk due to a possible decrease in blood pressure (patients with severe coronary heart disease or with hemodynamically significant cerebral vascular stenoses). In these cases, the dose can only be increased gradually.
Side effects of the drug Trental
Nausea, vomiting, heaviness in the epigastric region, diarrhea, headache, dizziness, aseptic meningitis (when taken in high doses), anxiety, sleep disturbances, facial flushing, flushing, tachycardia, angina pectoris, arterial hypotension, skin itching, rash, urticaria, angioedema, extremely rarely - anaphylactic shock. Very rarely, mainly when used simultaneously with anticoagulants or antiplatelet agents, bleeding (capillary from the skin and mucous membranes, gastrointestinal). The cause-and-effect relationship of bleeding with taking Trental has not been proven. In isolated cases, thrombocytopenia was observed.
Special instructions for the use of the drug Trental
The drug is prescribed with caution to patients with severe atherosclerosis of the cerebral and coronary vessels, especially with concomitant hypertension (arterial hypertension), heart rhythm disturbances, angina attacks, as well as patients with arterial hypotension or labile blood pressure. In these cases, the dose of the drug should be increased gradually, especially when administered parenterally. Caution is also required when prescribing the drug to patients with a history of peptic ulcers of the stomach and duodenum; patients who have recently undergone surgery. In these cases, the risk of bleeding is increased, so systematic monitoring of hemoglobin and hematocrit levels is necessary. Before prescribing Trental, patients with chronic heart failure should achieve circulatory compensation. For patients with labile or low blood pressure, patients at risk (severe coronary artery disease or severe stenosis of the main vessels of the brain), treatment should begin with the drug in low doses, select doses individually and increase them gradually, taking into account the tolerability of treatment. In patients with diabetes mellitus receiving insulin therapy or treatment with oral hypoglycemic agents, when using Trental in a high dose, the effect of these drugs on blood glucose levels may be enhanced. In these cases, the dose of insulin or oral hypoglycemic agents should be reduced and regular clinical monitoring should be carried out. If renal function is impaired (creatinine clearance 30 ml/min), the dose of the drug is selected individually, reducing it by approximately 30–50%. In case of severe liver failure, the dose of Trental should also be reduced depending on individual tolerability of the drug.
TRENTAL concentrate for the preparation of solution for infusion 20 mg/ml ampoule 5 ml No. 5
The dose and regimen of use are determined by the severity of circulatory disorders, as well as taking into account the individual tolerability of the drug and the characteristics of the patient. The drug is administered intravenously as an infusion 2 times a day, morning and afternoon. A single dose (per 1 infusion) is 200 mg of pentoxifylline (2 ampoules of 5 ml) or 300 mg of pentoxifylline (3 ampoules of 5 ml) in 250 ml or 500 ml of 0.9% sodium chloride solution or Ringer's solution. Compatibility with other infusion solutions should be tested separately; Only clear solutions can be used. The 100 mg dose should be administered but at least over 60 minutes. Depending on concomitant diseases (heart failure), it may be necessary to reduce the injected volume. In such cases, it is recommended to use a special infuser for controlled infusion. After the daily infusion, an additional 2 tablets may be prescribed. Trental 400. If 2 infusions are separated by a longer interval, then 1 tab. Trental 400 of the two additionally prescribed can be taken earlier (at approximately noon). If, due to clinical conditions, intravenous infusion is possible only once a day, an additional 3 tablets may be prescribed after it. Trentala 400 (2 tablets - at noon and 1 tablet - in the evening). Long-term intravenous infusion of Trental for 24 hours is indicated in more severe cases, especially in patients with severe pain at rest, with gangrene or trophic ulcers (stages III-IV according to Fontaine). The dose of Trental when administered parenterally over 24 hours, as a rule, should not exceed 1200 mg, while the individual dose can be calculated using the formula: 600 mcg/kg body weight per hour. The daily dose of the drug calculated in this way will be 1000 mg for a patient weighing 70 kg, and 1150 mg for a patient weighing 80 kg. In patients with renal failure (creatinine clearance less than 30 ml/min), it is necessary to reduce the dose by 30-50%, which depends on individual tolerability of the drug. In patients with severe liver dysfunction, a dose reduction is necessary taking into account individual tolerability of the drug. In patients with low blood pressure, as well as in people at risk due to a possible decrease in blood pressure (patients with severe coronary artery disease or with hemodynamically significant cerebral stenosis), treatment can be started in small doses, in these cases the dose should be increased gradually.
