Трентал®

General characteristics. Structure:

Active agent: пентоксифиллин - 20,00 mg.
Excipients: sodium chloride, water for injections.

Description: almost transparent colourless solution.

Pharmacological properties:

Pharmacodynamics. Trental improves rheological properties of blood (flowability) due to influence on patholologically the changed deformability of erythrocytes, inhibiting aggregation of thrombocytes and reducing the increased viscosity of blood. Trental improves microcirculation in zones of the broken blood circulation.
As active active ingredient Trental contains derivative xanthine - пентоксифиллин. The mechanism of its action is connected with inhibition of phosphodiesterase and accumulation of tsAMF in cells of smooth muscles of vessels and uniform elements of blood.
Having weak myotropic vazodilatiruyushchy effect, пентоксифиллин reduces the general peripheric vascular resistance a little and slightly expands coronary vessels.
Treatment by Trental leads to improvement of symptomatology of disturbances of cerebral circulation.
Success of treatment at occlusal damage of peripheral arteries (for example, the alternating lameness) is shown in lengthening of a distance of walking, elimination of night spasms in gastrocnemius muscles and disappearance of pains at rest.

Pharmacokinetics. Pentoksifillin is intensively metabolized in erythrocytes and a liver. Among the most known metabolites - a metabolite-1 (M-I; гидроксипентоксифиллин) the metabolite-4 (M-IV) and a metabolite-5 is formed due to splitting, and (M-V; карбоксипентоксифиллин) - due to oxidation of the main substance. M-I has the same pharmacological activity as пентоксифиллин. More than 90% of the accepted dose of a pentoksifillin are removed through kidneys and 3-4% with a stake.
The elimination half-life of a pentoksifillin after introduction of 100 mg intravenously made about 1,1 hours. At patients with heavy abnormal liver functions the elimination half-life of a pentoksifillin increases. Pentoksifillin has the large volume of distribution (168 l after the 30th minute infusion of 200 mg) and the high clearance making about 4500-5100 ml/min. Pentoksifillin and his metabolites do not contact proteins of a blood plasma. At a heavy renal failure removal of metabolites is slowed down.

Indications to use:

Disturbances of peripheric circulation of atherosclerotic genesis (including, the "alternating" lameness, a diabetic angiopatiya), trophic disturbances (including, trophic ulcers of a shin, gangrene), frostbites, a posttrombotichesky syndrome, etc.
Disturbances of cerebral circulation (effect of cerebral atherosclerosis: disturbances of concentration of attention, dizziness, memory impairment), ischemic and postinsultny states.
Disturbances of blood circulation in a retina and a choroid of an eye, an otosclerosis, degenerative changes against the background of pathology of vessels of an inner ear and decrease in hearing.

Route of administration and doses:

The dose and way of appointment are defined by weight of disturbances of blood circulation, and also on the basis of individual portability of drug.
The dosage is established by the doctor according to specific features of the patient.
The usual dose makes two intravenous infusions a day (in the morning and in the afternoon), each of which contains 200 mg of a pentoksifillin (2 ampoules on 5 ml) or 300 mg of a pentoksifillin (3 ampoules on 5 ml) in 250 ml or 500 ml of 0,9% of solution of sodium of chloride or Ringer's solution.
Compatibility with other infusion solutions has to be tested separately; it is possible to use only transparent solutions. 100 mg of a pentoksifillin have to be entered, at least, within 60 minutes. Depending on associated diseases (heart failure) there can be a need for reduction of the entered volumes. In such cases it is recommended to use a special infuzator for controlled infusion.
After day infusion 2 tablets of Trental 400 can be appointed in addition. If two infusions are divided by longer interval, then one tablet of Trental 400 of in addition appointed two, can be accepted earlier (approximately at noon).
If, owing to clinical conditions, performance of intravenous infusion is possible only once a day, in addition after it 3 tablets of Trental 400 can be appointed (2 tablets - at noon and 1 - in the evening).
Long intravenous infusion of Trental within 24 hours is shown in more hard cases, especially at patients with severe pains at rest, with gangrene or trophic ulcers (the III-IV stages on Fontena).
Trental dose entered parenterally within 24 hours, as a rule, should not exceed 1200 mg of a pentoksifillin, at the same time the individual dose can be counted on a formula: 0,6 mg of a pentoksifillin on weight kg an hour. The daily dose counted thus will make 1000 mg of a pentoksifillin for the patient weighing 70 kg and 1150 mg of a pentoksifillin for the patient weighing 80 kg.
At patients with a renal failure (the clearance of creatinine is lower than 30 ml/min.) it is necessary to lower a dosage by 30%-50% that depends on individual portability of drug the patient.
Reduction of a dose, taking into account individual portability, is necessary at patients with a heavy abnormal liver function.
Treatment can be begun with small doses at patients with low arterial pressure, and also at the persons which are in risk group in view of possible pressure decrease (patients with a severe form of an ischemic heart disease or with hemodynamically significant stenoses of vessels of a brain). In these cases the dose can be increased only gradually.

Features of use:

Treatment should be carried out under control of arterial pressure.
At the patients with a diabetes mellitus accepting hypoglycemic means, purpose of high doses can cause the expressed hypoglycemia (dose adjustment is required).
At appointment along with anticoagulants it is necessary to watch indicators of coagulant system of blood carefully.
At the patients who recently transferred an operative measure systematic control of level of hemoglobin and a hematocrit is necessary.
The entered dose has to be reduced at patients with low and unstable arterial pressure.
At elderly people reduction of a dose (increase in bioavailability and reduction in the rate of removal) can be required.
Safety and efficiency of a pentoksifillin at children are studied insufficiently.
Smoking can reduce a therapeutic effectiveness of drug. Compatibility of solution of a pentoksifillin with infusion solution should be checked in each case.
When performing intravenous infusions of the patient has to be in a prone position.

Side effects:

In cases when Trental is used in high doses or at a high speed of infusion, there can sometimes be following side effects:
from a nervous system: headache, dizziness, uneasiness, sleep disorders, spasms;
from integuments and podkozhnozhirovy cellulose: a dermahemia of the person, "inflows" of blood to face skin and an upper part of a thorax, hypostases, the increased fragility of nails;
from the alimentary system: xerostomia, anorexia, intestines atony;
from a cardiovascular sitema: tachycardia, arrhythmia, cardialgia, progressing of stenocardia, lowering of arterial pressure;
from system of a hemostasis and bodies of a hemopoiesis: a leukopenia, thrombocytopenia, a pancytopenia, bleedings from vessels of skin, mucous membranes, a stomach, intestines, a hypofibrinogenemia;
from sense bodys: vision disorder, scotoma;
allergic reactions: itch, dermahemia, small tortoiseshell, Quincke's disease, acute anaphylaxis.
Very seldom cases of development of aseptic meningitis, an intra hepatic cholestasia and increase in activity of "hepatic" transaminases, an alkaline phosphatase meet.

Interaction with other medicines:

Pentoksifillin is capable to strengthen action of the means reducing the arterial pressure (APF inhibitors, nitrates).
Pentoksifillin can strengthen effect of the medicines influencing coagulant system of blood (indirect and direct anticoagulants, trombolitik), antibiotics (including cephalosporins).
Cimetidinum increases concentration of a pentoksifillin in plasma (risk of emergence of side effects).
Joint appointment with other xanthines can lead to excessive nervous excitement.
Antihyperglycemic effect of insulin or peroral anti-diabetic means can be strengthened at reception of a pentoksifillin (the increased risk of development of a hypoglycemia). Strict control of such patients is necessary.
Some patients have a concomitant use of a pentoksifillin and theophylline can lead to increase in level of theophylline. It can lead to increase or strengthening of the side effects connected with theophylline.

Contraindications:

• hypersensitivity to a pentoksifillin, other methylxanthines or to any of drug components;
• massive bleedings;
• extensive retinal apoplexies of an eye;
• hematencephalons;
• acute myocardial infarction;
• heavy arrhythmias;
• crushing atherosclerotic damages of coronary or brain arteries;
• uncontrollable arterial hypotension;
• age up to 18 years;
• pregnancy, lactation period.
With care drug should be used at patients with: arterial hypotension (risk of a lowering of arterial pressure), chronic heart failure, an impaired renal function (the clearance of creatinine is lower than 30 ml/min.) (risk of accumulation and the increased risk of development of side effects), heavy abnormal liver functions (risk of accumulation and the increased risk of side effects), the increased tendency to bleeding, including, as a result of use of anticoagulants or at disturbances in system of a blood coagulation (risk of development of heavier bleedings), after recently postponed operative measures.

Overdose:

Overdose symptoms: weakness, perspiration, nausea, cyanosis, dizziness, a lowering of arterial pressure, tachycardia, an unconscious condition, drowsiness or excitement, arrhythmia, a hyperthermia, an areflexia, a loss of consciousness, toniko-clonic spasms, symptoms of gastrointestinal bleeding (vomiting like a coffee thick).
Symptomatic treatment: the special attention has to be directed to maintenance of arterial pressure and function of breath. Convulsive attacks stop administration of diazepam.
At emergence of the first signs of overdose immediately stop administration of drug. Provide lower position of the head and an upper part of a trunk.

Storage conditions:

To store in the place protected from light at a temperature from 8 °C to 25 °C.
To store in the place, unavailable to children! List B. Period of validity 4 years. After a period of validity drug cannot be used.

Issue conditions:

According to the recipe

Packaging:

Concentrate for preparation of solution for infusions of 20 mg/ml.
On 5 ml in ampoules of transparent, colourless glass (type I) with a break point.
On 5 ampoules in a plastic blister strip packaging without covering (pallet).
On 1 pallet together with the application instruction in a cardboard pack.